Clearly, the reliability of the relative affinity of a candidate ligand relies on the validity of Eq.(6), and requires the simultaneous satisfaction of the following prerequisites for the pair of the candidate ligand and its reference ligand. (a) The candidate ligand and its reference ligand bind to the same site(s) on the target. In practice, the binding site(s) of the candidate ligand can be judged based on its competitive binding against a reference ligand but can not be optimized. (b) The candidate ligand and its reference ligand, in both the PMFS and the concentrated extract, produce peak areas within their own linear ranges. (c) The candidate ligand and its reference ligand, in both the PMFS and the concentrated extract, produce peak areas over five times the absolute values of their own intercepts of linear response. (d) The candidate ligand and its reference ligand have binding ratios of below 10% in the competitive binding system. All the later three prerequisites should be met by ...
Ligand binding assays (LBA) is an assay, or an analytic procedure, whose procedure or method relies on the binding of ligand molecules to receptors, antibodies or other macromolecules. A detection method is used to determine the presence and extent of the ligand-receptor complexes formed, and this is usually determined electrochemically or through a fluorescence detection method. This type of analytic test can be used to test for the presence of target molecules in a sample that are known to bind to the receptor. There are numerous types of ligand binding assays, both radioactive and non-radioactive. As such, ligand binding assays are a superset of radiobinding assays, which are the conceptual inverse of radioimmunoassays (RIA). Some newer types are called "mix-and-measure" assays because they do not require separation of bound ligands. Ligand binding assays are used primarily in pharmacology for various demands. Specifically, despite the human bodys endogenous receptors, hormones, and other ...
TY - CHAP. T1 - Induction of cell adhesion and cell spreading by various cell surface ligands. AU - Grinnell, F.. PY - 1977. Y1 - 1977. UR - http://www.scopus.com/inward/record.url?scp=17344391658&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=17344391658&partnerID=8YFLogxK. M3 - Chapter. AN - SCOPUS:17344391658. VL - 6. BT - Journal of Supramolecular and Cellular Biochemistry. ER - ...
Glyconanomaterials, nanomaterials carrying multiple carbohydrate ligands, provide an excellent platform for sensitive protein recognition. Using nanomaterials as the scaffold, multivalent interactions between glycan ligands and proteins have been demonstrated. However, the quantitative analysis of the binding affinity of these glyconanomaterials has been lacking. In this Article, we report a new method to measure the binding affinity of glyconanoparticle (GNP)-protein interactions based on a fluorescent competition binding assay, which yielded the apparent dissociation constant (K-d) of GNPs with the interacting protein. Au nanoparticles conjugated with underivatized mono-, oligo-, and polysaccharides were synthesized using our recently developed photocoupling chemistry. The affinities of these GNPs with lectins were measured and were several orders of magnitude higher than the corresponding free ligands with lectins. The effect of ligand display on the binding affinity of GNPs was, furthermore, ...
PREFACE TO THE SIXTH EDITION. ABBREVIATIONS.. 1. Applications in Coordination Chemistry.. 1.1. Ammine, Amido, and Related Complexes.. 1.2. Complexes of Ethylenediamine and Related Ligands.. 1.3. Complexes of Pyridine and Related Ligands.. 1.4. Complexes of Bipyridine and Related Ligands.. 1.5. Metalloporphyrins.. 1.6. Metallochlorins, Chlorophylls, and Metallophthalocyanines.. 1.7. Nitro and Nitrito Complexes.. 1.8. Lattice Water and Aquo and Hydroxo Complexes.. 1.9. Complexes of Alkoxides, Alcohols, Ethers, Ketones, Aldehydes, Esters, and Carboxylic Acids.. 1.10. Complexes of Amino Acids, EDTA, and Related Ligands.. 1.11. Infrared Spectra of Aqueous Solutions.. 1.12. Complexes of Oxalato and Related Ligands.. 1.13. Complexes of Sulfate, Carbonate, and Related Ligands.. 1.14. Complexes of b-Diketones.. 1.15. Complexes of Urea, Sulfoxides, and Related Ligands.. 1.16. Cyano and Nitrile Complexes.. 1.17. Thiocyanato and Other Pseudohalogeno Complexes.. 1.18. Complexes of Carbon Monoxide.. 1.19. ...
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Multivalency achieves strong, yet reversible binding by the simultaneous formation of multiple weak bonds. It is a key interaction principle in biology and promising for the synthesis of high-affinity inhibitors of pathogens. We present a molecular model for the binding affinity of synthetic multivalent ligands onto multivalent receptors consisting of n receptor units arranged on a regular polygon. Ligands consist of a geometrically matching rigid polygonal core to which monovalent ligand units are attached via flexible linker polymers, closely mimicking existing experimental designs. The calculated binding affinities quantitatively agree with experimental studies for cholera toxin (n = 5) and anthrax receptor (n = 7) and allow to predict optimal core size and optimal linker length. Maximal binding affinity is achieved for a core that matches the receptor size and for linkers that have an equilibrium end-to-end distance that is slightly longer than the geometric separation between ligand core ...
This invention is directed to a ligand-receptor assay for determining the presence of at least one target ligand, capable of competing with a ligand analogue conjugate for binding sites available on a ligand receptor, said ligand analogue conjugate comprising at least one ligand analogue coupled to a colloidal gold particle, in a fluid sample suspected of containing said target ligand comprising the steps of: a. contacting said fluid sample with said ligand analogue conjugate and said ligand receptor to form a homogeneous reaction mixture, the relative amounts of said ligand analogue conjugate and said ligand receptor being selected such that in the absence of said target ligand and subsequent to substantially equilibrium binding in said reaction mixture, substantially all of said ligand analogue conjugate is bound to said ligand receptor such that no unbound ligand analogue conjugate is detected as a result of the assay method; b. detecting unbound ligand analogue conjugates in said reaction mixture by
Antagonist-bound closed state GluA2 density map quality and resolutiona,b, GluA2em antagonist-bound closed state density map with coordinates for ATD dimers, LB
The new β2 Adrenoceptor (β2AR) crystal structures provide a high-resolution snapshot of receptor interactions with two particular partial inverse agonists, (−)-carazolol and timolol. However, both...
article{8565564, abstract = {Currently, there is mounting evidence that intermolecular receptor-receptor interactions may result in altered receptor recognition, pharmacology and signaling. Heterobivalent ligands have been proven useful as molecular probes for confirming and targeting heteromeric receptors. This report describes the design and synthesis of novel heterobivalent ligands for dopamine D-2-like receptors (D-2-likeR) and the -opioid receptor (OR) and their evaluation using ligand binding and functional assays. Interestingly, we identified a potent bivalent ligand that contains a short 18-atom linker and combines good potency with high efficacy both in -arrestin2 recruitment for OR and MAPK-P for D4R. Furthermore, this compound was characterized by a biphasic competition binding curve for the D4R-OR heterodimer, indicative of a bivalent binding mode. As this compound possibly bridges the D4R-OR heterodimer, it could be used as a pharmacological tool to further investigate the ...
In case functional assays are available TriCEPS coupled ligands can also be tested to see if a similar output is achievable with a TriCEPS coupled ligand compared to a ligand that is not coupled to TriCEPS.. In addition, TriCEPS V2.0 can be utilized as Flow Cytometry (FACS) reagent for detecting binding of primary amine containing molecules to cells.. As first step, the TriCEPS v.2.0 molecule is coupled to the ligand of interest (peptide, protein, Antibody, ADC or other primary amine containing molecules) and to the positive control ligand (e.g. transferrin) and negative control ligand (e.g. glycine). This coupling reaction is tested with Dot blot to assess if the coupling worked.. Then, the TriCEPS coupled ligands are then added to the non-oxidized cells to show that the ligand binds to the unknown targets at the cell surface and TriCEPS does not interfere with the ligand receptor interaction.. Flow Cytometry tests with TriCEPS coupled ligand on oxidized cells can be further performed to test ...
Binding Affinity Prediction of Protein-Ligand complex containing Zinc [ BAPPL-Z ] server computes the binding free energy of a zinc containing metalloprotein-ligand complex using an all atom energy based empirical scoring function
Recently the first community-wide assessments of the prediction of the structures of complexes between proteins and small molecule ligands have been reported in the so-called GPCR Dock 2008 and 2010 assessments. In the current review we discuss the different steps along the protein-ligand modeling workflow by critically analyzing the modeling strategies we used to predict the structures of protein-ligand complexes we submitted to the recent GPCR Dock 2010 challenge. These representative test cases, focusing on the pharmaceutically relevant G Protein-Coupled Receptors, are used to demonstrate the strengths and challenges of the different modeling methods. Our analysis indicates that the proper performance of the sequence alignment, introduction of structural adjustments guided by experimental data, and the usage of experimental data to identify protein-ligand interactions are critical steps in the protein-ligand modeling protocol.
Background: Using the popular program AutoDock, computer-aided docking of small ligands with 6 or fewer rotatable bonds, is reasonably fast and accurate. However, docking large ligands using AutoDocks recommended standard docking protocol is less accurate and computationally slow. Results: In our earlier work, we presented a novel AutoDock-based incremental protocol (DINC) that addresses the limitations of AutoDocks standard protocol by enabling improved docking of large ligands. Instead of docking a large ligand to a target protein in one single step as done in the standard protocol, our protocol docks the large ligand in increments. In this paper, we present three detailed examples of docking using DINC and compare the docking results with those obtained using AutoDocks standard protocol. We summarize the docking results from an extended docking study that was done on 73 protein-ligand complexes comprised of large ligands. We demonstrate not only that DINC is up to 2 orders of magnitude ...
While human and mouse genetics consistently have unveiled various physiological roles of members of the pGC family, overall the mode of ligand‐dependent as well as ligand‐independent activation of these transmembrane enzymes leading to intracellular cGMP synthesis remains enigmatic. The intracellular region of pGCs consists of a juxtamembranous protein kinase-homology domain, an amphipathic α‐helical or hinge region, and the C‐terminal cyclase catalytic domain (Fig 1) (reviewed by Potter, 2011). The hinge region is involved in higher order oligomerization. Hence, although pGCs contain a single cyclase site per polypeptide chain, receptor dimerization is essential for the activation of this cGMP‐synthesizing domain (Potter, 2011). The crystal structures of the extracellular domain of GC‐A, in complex with atrial natriuretic peptide, or in absence of the ligand, suggested that hormone binding induces a rotation of the juxtamembrane domains, which is transmitted across the ...
The use of surrogates either as native orthologous proteins or as optimized chimeras, which can be readily crystallized and soaked with small molecules, has been validated by its success in other fields, particularly in guiding kinase inhibitor development (Ikuta et al., 2001; Breitenlechner et al., 2004). One should bear in mind, however, that the surrogate approach has its limitations, and local structural differences may have considerable effect on ligand binding (Davies et al., 2007). HIV-1 and PFV INs are fully orthologous, with identical canonical domain folds and stoichiometry. Fortuitously, all intasome atoms (protein, DNA, metal ions) that are in contact with the soaked INSTI molecules are invariant between HIV-1 and PFV (Hare et al., 2010a). Thus, we expect that structural differences between HIV-1 and PFV intasomes that are directly relevant to INSTI binding will be small. An unbiased test of this idea can be made by comparing the active sites in isolated catalytic core domains from ...
Recently, N,N-trans Re(O)(LN-O)2X (LN-O = monoanionic N-O chelates; X = Cl or Br prior to being replaced by solvents or alkoxides) complexes have been found to be superior to the corresponding N,N-cis isomers in the catalytic reduction of perchlorate via oxygen atom transfer. However, reported methods for Re(O)(LN-O)2X synthesis often yield only the N,N-cis complex or a mixture of trans and cis isomers. This study reports a geometry-inspired ligand design rationale that selectively yields N,N-trans Re(O)(LN-O)2Cl complexes. Analysis of the crystal structures revealed that the dihedral angles (DAs) between the two LN-O ligands of N,N-cis Re(O)(LN-O)2Cl complexes are less than 90°, whereas the DAs in most N,N-trans complexes are greater than 90°. Variably sized alkyl groups (−Me, −CH2Ph, and −CH2Cy) were then introduced to the 2-(2′-hydroxyphenyl)-2-oxazoline (Hhoz) ligand to increase steric hindrance in the N,N-cis structure, and it was found that substituents as small as −Me ...
In the case of the CaM-CaMKK complex, we obtained a set of desired near-native decoys with lowest interaction energy (Figure 3) and high Tc-IFPs (Figure 4). These results are explained by the structure of the CaM-CaMKK complex, which is different from those of the CaM-CNG and CaM-PMCA complexes. The globular cognate structure of CaM in the CaM-CaMKK complex differed only slightly from that of the CaM-CNG complex, indicating that the cavity of the CaM-CaMKK complex is narrower than that of the CaM-CNG complex, as shown in Figure 2. In contrast to the simple alpha helical structure of the CNG and PMCA ligand peptides, the CaMKK ligand peptide has an additional loop region in the C-terminal end. These structural features of the ligand have contributed in obtaining a set of near-native decoys for the CaM-CaMKK complex. In context with the shape of the ligand peptide, it is noteworthy that we found CaM-CNG b-decoys in which the CNG was bound to the CaM cavity in an inverse manner as compared to the ...
A soluble factor produced by HTU-34 cells is responsible for αvβ3 ligand-binding activity and recruitment to FCs. (A) Adhesion assay. Treatment of HTU-34 cel
Hi, When you say wrong postion, what does it mean? are the 2 ligands you are trying to refine being pushed away from each other? If that is the case first thing I would check is the ALTLOC comlumn of their pdb file entries. Make sure one is ALTLOC A and the other ALTLOC B. I have refined with ligands in four different positions before using phenix before and got satisfactory results... Hope this helps, -- Yuri Pompeu ...
The fact that over 30% of current pharmaceuticals target heptahelical G protein-coupled receptors (GPCRs) attests to their tractability as drug targets. While GPCR drug development has traditionally focused on conventional agonists and antagonists, the growing appreciation that GPCRs mediate physiologically relevant effects via both G protein and non-G protein effectors has prompted the search for ligands that can bias downstream signaling in favor of one or the other process. Biased ligands are novel entities with distinct signaling profiles dictated by ligand structure, and the potential prospect of biased ligands as better drugs has been pleonastically proclaimed. Indeed, preclinical proof-of-concept studies have demonstrated that both G protein and arrestin pathway-selective ligands can promote beneficial effects in vivo while simultaneously antagonizing deleterious ones. But along with opportunity comes added complexity and new challenges for drug discovery. If ligands can be biased, then ...
Carroll, F., Blough, B., Mascarella, S., Xu, H., Goodman, C. B., & Rothman, R. B. (1993). Synthesis and Ligand Binding at PCP Sites 1 and 2 for Hexahydro-2-substituted-1-methylindeno[1,2-b]pyrroles. Medicinal Chemistry Research, 3, 178 ...
The Rho GTPases are known regulators of the actin cytoskeleton and affect multiple cellular activities including cell morphology, polarity, migration, proliferation and apoptosis, phagocytosis, cytokinesis, adhesion, vesicular transport, transcription, and neurite extension and retraction. Like DOCK2, DOCK8 is likely to regulate the activity of GTPases and thus be involved in cytoskeletal changes associated with various cellular processes. DOCK8 is proposed to serve as an effector downstream of CD19 and PI3K to promote G protein signaling events critical for integrin polarization at the synapse and for the survival of marginal zone B cells and germinal center (GC) B cells. During a T cell-dependent humoral immune response, CD4+ T helper cell subsets including TFH, Th1 and Th2 cells migrate to the T cell/B cell borders in secondary lymphoid organs, and interact with cognate antigen-specific B cells through the pairing of T cell and B cell surface ligands and receptors such as CD40 with its ligand ...
Low-affinity ligands can be efficiently optimized into high-affinity drug leads by structure based drug design when atomic-resolution structural information on the protein/ligand complexes is availabl
The problem with method #1 is that it is very labor intensive, and that any compound proposed may be difficult and/or expensive to acquire. The problem with approach #2 is that the compounds may still be difficult to acquire, although there are strategies to overcome this limitation. It can also be, relatively speaking, slow. The third approach, docking, is the one taken by DOCK and its graphical user interface, DOCK Blaster. It is particularly pragmatic when used to screen a database of compounds that can be acquired rapidly, such as those in ZINC, because the time from hypothesis to experimental test can be very short, and the project can progress rapidly. ...
Ligand binding affinities at G-protein coupled receptors (GPCRs) have historically been determined using a radioligand that competes for receptor binding sites against an unlabeled drug-like compound. But the potential hazards of open-source radioisotope handling, and the environmental impact of radioisotope disposal, make this a less desirable and costly technology. Therefore, new fluorescent based alternatives have been developed to replace radioligands.
Aspartate mutation distinguishes ETA but not ETB receptor subtype-selective ligand binding while abolishing phospholipase C activation in both receptors.: The e
Photoaffinity cross‐linking is a rapidly developing technology for studying biomolecular interactions, including protein ligand‐receptor binding
One of the major challenges in the field of system biology is to understand the interaction between a wide range of proteins and ligands. In the past, methods have been developed for predicting binding sites in a protein for a limited number of ligands.. ...
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Structural and Dynamical Insight into PPARγ Antagonism: In silico Study of the Ligand-Receptor Interactions of non-Covalent Antagonists
A method is disclosed for coupling a ligand within a porous support. The method involves mixing ligand and porous support under conditions sufficient to suppress coupling conditions of the ligand to the porous support while enhancing the relative rate of diffusion, to the rate of reaction, of the ligand into and within the porous support, and then altering the conditions to enhance rapid coupling of the ligand within the porous support. The alteration from diffusion conditions to coupling conditions involves a change in the reaction solution of pH, ionic strength, temperature, coupling competitor, such that a relatively lower Thiele Modulus during diffusion conditions changes to a relatively higher Thiele Modulus during coupling conditions. Derivatized porous supports produced according to the method are also disclosed. The derivatized porous support has enhanced functional efficiency. Derivatized porous supports prepared from azlactone-functional porous supports are also disclosed ...
Users can interactively analyze protein-small ligand binding modes with statistically determined interaction patterns rather than relying on a priori knowledge of the users.
Bishwa I am using Phenix 1.0-1069 for refinement and coot 0.7-pre-1 for , visualization , and rebuilding. I used SMILES in coot to build the ligand and then merged , them , with PDB.I had to do this as a separate step for both chains and the .cif , file , so produced was not accepted for refinement. , Why? Can you send me the files directly? , , I used readyset to obtain the restrains for refinement using .pdb file, , even , though my refinement works, when i try to run real build refine in coot I , get , this error message: , It would be better to generate the restraints using the SMILES in eLBOW and then pass the restraints file to ReadySet!. Send me the file and we can fix them Nigel NB. Any files sent to me will be held in strictest confidence. , , Failed to match (to the dictionary) the following model atom names: , HB3 , "O6" "C10" "C11" "C12" "O7" "C13" "O5" "C8" "C9" ...... , That would cause exploding atoms, so the refinement didnt start. , , Could someone help me with fixing this ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology. ...
The interaction between cells and extracellular matrix HA is clearly of fundamental importance both during embryonic limb development and in processes such as wound healing and inflammation in later adult life (19-22). Such importance predicts that many receptors must be involved in HA adhesion, and that complex mechanisms must exist to regulate both their expression and their ligand-binding affinity. Yet at present, the list of professional cell surface HA receptors is small and includes only the CD44 molecule, RHAMM, and the LEC HA receptors. Furthermore, deletion of the gene for CD44, the most abundant and widely expressed of these, has little if any deleterious effects on the embryo (43). Thus, it has become increasingly clear to many workers in the field that additional receptors for HA are likely to exist within the genome.. In this paper we have described the primary structure and biological function of one such receptor, termed LYVE-1, which is present within vessels of the lymphatic ...
We developed models for physically realistic consecutive and independent binding schemes and compared them with the Hill equation (Figure 1). It follows from this comparison that the "half-effect" concentration may significantly differ from the conventional Hill equation depending on the binding mechanism. We used our models to rigorously investigate mechanisms for second messenger activation by multisite proteins. We show that differential and selective activation of different targets by the same protein-ligand complex (Ca2+ and calmodulin, for example) can be achieved by biologically active non-saturated intermediate multisite protein-ligand complexes. ...
For downstream processes that utilize a Praesto® Jetted A50 capture step, Repligen offers the only kit on the market that includes the NGL-Impact™ A Ligand standard for the most accurate quantitation. Exact matched Protein A reference standard (NGL-Impact™ A Ligand) Sensitivity of 0.1 ng/mL Recovery: 80-120% Accuracy &
Binding Affinity Prediction of Protein-Ligand complex containing Zinc [ BAPPL-Z ] server computes the binding free energy of a zinc containing metalloprotein-ligand complex using an all atom energy based empirical scoring function
As for primary fragment screening, I encourage a project teams to use bio-assay when possible. Certainly not all assays are able to reliably detect weak ligands and many suffer from background interference of colored or fluorescent compounds at high concentration. In some cases the use of a "kinetic read" helps with this. I then advocate follow-up with a biophysical assay such as NMR-STD, biacore, or ITD-calorimetry. In cases where the bioassay is not reliable and protein is abundantly available, you can reverse the order to put the biophysical assay first. In both cases, keep the X-ray step toward the end when there is a short list of validated hits with high ligand efficency, and solubility about 10-times above Kd. ...
CiteSeerX - Scientific articles matching the query: Analysis of Cellular Proliferation and Survival Signaling by Using Two Ligand/Receptor Systems Modeled by Pathway Logic.
2M0P: Gentamicin binds to the megalin receptor as a competitive inhibitor using the common ligand binding motif of complement type repeats: insight from the nmr structure of the 10th complement type repeat domain alone and in complex with gentamicin.
In downstream purification of monoclonal antibodies (MAbs), the single greatest contributor to manufacturing costs is the expensive capture step typically based on protein A affinity chromatography. Almost since its introduction to bioprocessing, efforts have been made to reduce the cost of this step. Several alternative ligands have been promulgated as potential replacements for protein A, but they have proven difficult to adopt and scale up. Supplier companies have pushed for increases in capacity and economics, but those are always accompanied…. ...
A wrapper is defined as a carbon atom not bonded directly to an oxygen or nitrogen atom, i.e. a non-polar carbon atom. The plugin count as wrappers any non-polar carbon from any protein chain, organic ligand or other type of molecule, if the atoms belong "selection" (see below). This means that if you have, for example, a dimeric protein you will probably get different results for the dimer and for the isolated monomers. Instead, if you upload two (or more) different files the results will be independent because the plugin does not count atoms from other objects ...
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
Hamster Monoklonal CD40 Ligand Antikörper für BP, FACS, Neut. Jetzt diesen anti-CD40 Ligand Antikörper bestellen. | Produkt ABIN4260972
most probably you have not selected the first ligand in the first step of the protein setup in the Heteroatoms box in the second docking. You must select the ligand if you want it to keep it during the docking. If it is not the problem, please share the url of the docking in question ...
NOTE: The prediction model might be improved by removing some chemicals from the superposition in Step 1. It might be a subjective call as to which chemicals are good for the model and which ones should be removed. In some cases a crystal structure of a protein-ligand complex is available and the ligand pose would be a good template to superimpose onto ...
Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) announces the acquisition of economic rights to multiple programs owned by CorMatrix®. Ligand will
2ZQ1: Congeneric but still distinct: how closely related trypsin ligands exhibit different thermodynamic and structural properties
Here we report on the structure-based optimization of antibody-recruiting molecules targeting HIV gp120 (ARM-H). These studies have leveraged a combination of medicinal chemistry, biochemical and cellular assay analysis, and computation. Our findings have afforded an optimized analog of ARM-H, which is ∼1000
A new series of platinacyclopentanes (2a-2f) and platinacycloheptanes (3a-3f) of the type [Pt(N^P)(CH2)n] (n = 4, 6) were obtained by the reaction of [Pt(COD)(CH2)n] with the appropriate iminophosphine ligand (1a-1f). These complexes were characterised using a variety of spectroscopic and analytical techniqu
Gentaur molecular products has all kinds of products like :search , Reliatech \ Anti_Mouse, mab Flt_3 Ligand Source Rat \ 103-M383 for more molecular products just contact us
Cool! By the way - The experimental names result of generating the name based on the 3d-prepared ligand, yes? Why not use the unprepared 2d-model, then the name would be correct and not interfered with the PM6 calculations ...
reference: Conformation of a peptide ligand bound to its G-protein coupled receptor., Inooka H, Ohtaki T, Kitahara O, Ikegami T, Endo S, Kitada C, Ogi K, Onda H, Fujino M, Shirakawa M, Nat Struct Biol 2001 Feb;8(2):161-5. PMID: 11175907 ...
A free platform for explaining your research in plain language, and managing how you communicate around it - so you can understand how best to increase its impact.
Looks for amino acid and/or nucleotide patterns and/or small ligands coordinated to a given prosthetic centre. Files have to be in the local file system and contain proper extension.. ...
Note that if all you are doing is simulating some weird ligand in water, or some weird ligand with a normal protein, then the above is more work than generating a standalone .itp file containing a [moleculetype] (for example, by modifying the .top produced by some parameterization server), and inserting an #include of that .itp file into a .top generated for the system without that weird ligand.. ...
A free platform for explaining your research in plain language, and managing how you communicate around it - so you can understand how best to increase its impact.
... Column Selection - Variety Gives You The Power Of Optimization Rezex columns utilize different ligands.
EGFR is the cell-surface receptor for members of the epidermal growth factorfamily (EGF-family) of extracellular protein ligands.
This form allows you to request diffs between any two revisions of this file. For each of the two "sides" of the diff, select a symbolic revision name using the selection box, or choose Use Text Field and enter a numeric revision. ...
This form allows you to request diffs between any two revisions of this file. For each of the two "sides" of the diff, select a symbolic revision name using the selection box, or choose Use Text Field and enter a numeric revision. ...
We perform a large-scale study of intrinsically disordered regions in proteins and protein complexes using a nonredundant set of hundreds of different protein complexes. has been associated with particular functions including cell regulation; signaling; and protein, DNA, and ligand binding. Many proteins are intrinsically disordered in native form and fold upon binding, following the conventional […]. ...
Inorganic self-assembly through sequential complexation in the formation of bimetallic and trimetallic architectures from multisite ligands based on 5,5-disubstituted 2,2-bipyridines ...
Atomically precise gold nanoclusters are ideal model catalysts with well-defined compositions and tunable structures. Determination of the ligand effect on catalysis requires the use of gold nanoclusters with protecting ligands as the only variable. Two isostructural Au38 nanoclusters, [Au38(L)20(Ph3P)4]2+ (L = alkynyl or thiolate), have been synthesized by a direct reduction method, and they have an unprecedented face-centered cubic (fcc)-type Au34 kernel surrounded by 4 AuL2 staple motifs, 4 Ph3P, and 12 bridging L ligands. The Au34 kernel can be derived from the fusion of two fcc-type Au20 via sharing a Au6 face. Catalytic performance was studied with these two nanoclusters supported on TiO2 (1/TiO2 and 2/TiO2) as catalysts. The alkynyl-protected Au38 are very active (,97%) in the semihydrogenation of alkynes (including terminal and internal ones) to alkenes, whereas the thiolated Au38 showed a very low conversion (,2%). This fact suggests that the protecting ligands play an important role in ...
Protein-ligand binding site prediction from a 3D protein structure plays a pivotal role in rational drug design and can be helpful in drug side-effects prediction or elucidation of protein function. Embedded within the binding site detection problem is the problem of pocket ranking - how to score and sort candidate pockets so that the best scored predictions correspond to true ligand binding sites. Although there exist multiple pocket detection algorithms, they mostly employ a fairly simple ranking function leading to sub-optimal prediction results. We have developed a new pocket scoring approach (named PRANK) that prioritizes putative pockets according to their probability to bind a ligand. The method first carefully selects pocket points and labels them by physico-chemical characteristics of their local neighborhood. Random Forests classifier is subsequently applied to assign a ligandability score to each of the selected pocket point. The ligandability scores are finally merged into the resulting
The Gpr1 G protein-coupled receptor regulates filamentous growth: Our studies reveal that the G protein-coupled receptor Gpr1 regulates pseudohyphal differentiation in S. cerevisiae (Figure 9). The Gpr1 receptor also regulates invasive growth of haploid strains and is required for expression of the FLO11 gene encoding a cell surface flocculin. The phenotypes of mutant strains lacking the Gpr1 receptor are similar to those of mutant strains lacking the Gα protein Gpa2, and genetic evidence supports a model in which ligand binding to the Gpr1 receptor activates Gpa2p via a direct interaction. The downstream elements of this signaling pathway consist of adenylyl cyclase, which is activated by Gpa2p to produce cAMP (Nakafukuet al. 1988; Colomboet al. 1998), resulting in activation of PKA (Figure 9). Recent studies have revealed that the Tpk2 catalytic subunit of PKA regulates pseudohyphal differentiation via the Sfl1 and Flo8 transcription factors that regulate expression of the cell surface ...
Easily label your own tag ligands & other small molecules. Mix-n-Stain™ CF® dye small ligand labeling kits are designed for rapid labeling of small (MW ~ 150 - 5,000) and relatively high affinity biological ligands (or substrates). Labeling takes about 30 minutes, without a final purification step. The ligands to be labeled must contain an aliphatic amine group that is not required for biological activity of the ligand. The amine group will form a covalent linkage with the reactive CF® dye provided in the kit. For example, suitable ligands or substrates include SNAP-tag®, CLIP-tag™ and HaloTag® ligands with an aliphatic amine. Many other small ligands are also possible candidates if they meet the criteria described above.. Simply mix your small molecule ligand with the reaction buffer and the optimally formulated dye provided, and incubate for 30 minutes, followed by a brief 5 minute quenching step. No reactive Mix-n-Stain™ dye is available at the end of labeling; therefore the ...
Studies to date have shown that EGFR activation by GPCRs represents a paradigm of potential cross-talk between tyrosine kinase receptors and GPCRs (31) . Although the biological significance of the initial studies performed in fibroblasts was undetermined, subsequent investigations in cancer cells have shown that activation of EGFR by GPCR ligands leads to downstream MAPK activation, tumor cell invasion, and DNA synthesis (13 , 32) . We previously reported that HNSCC cell lines and tissues express increased levels of GRP and GRPR when the levels of GRPR in the primary tumor were correlated with patient survival (16) . Additional investigation showed that blockade of GRP using the neutralizing antibody 2A11 inhibited HNSCC growth in vitro and in vivo, thus implicating an autocrine regulatory pathway involving this GPCR ligand and receptor in HNSCC (16) . The importance of EGFR up-regulation in HNSCC carcinogenesis has been well documented (5 , 6 , 33 , 34) . Additional investigation showed that ...
BioAssay record AID 353554 submitted by ChEMBL: Inhibition of DHT binding to human recombinant androgen receptor ligand binding domain at 15 uM by fluorescence polarization.
The EGF 5 receptor is a Mr 170,000 plasma membrane glycoprotein composed of an extracellular ligand-binding domain, a transmembrane lipophilic segment, and an intracellular protein kinase domain with a regulatory COOH-terminal segment (1) . After ligand binding, EGF-receptor dimerization occurs, which results in high-affinity ligand binding, activation of the intrinsic protein tyrosine kinase activity, and tyrosine autophosphorylation (1) . These events lead to activation of a cascade of biochemical and physiological responses that are involved in the mitogenic signal transduction of cells (2) . Extensive preclinical studies (2 , 3) have shown that these downstream signaling transduction cascades regulate multiple cellular processes such as proliferation, differentiation, survival, and transformation.. Several lines of evidence support the EGF receptor as a target for therapy of head and neck carcinomas. EGF receptor and one of its ligands, TGF-α, are overexpressed in the majority of head and ...
The results of the present work showed that administration of ERα-subtype-selective ligand PPT (Stauffer et al. 2000) in ovariectomized rats had oestrogen activity on all parameters of gonadotrope function analysed, whereas administration of ERβ-subtype-selective ligand DPN (Meyers et al. 2001) mimicked all actions of PPT except the reduction of pituitary content and serum concentration of LH. The latter action, however, was the only one not affected when both ER ligands were administered simultaneously. Morphological parameters of gonadotrope function evaluated were qualitative characteristics of the membrane-enclosed intracellular organelles, gonadotrope size, and PR expression status. In fact, due to the pivotal role of PR in gonadotrope function in the rat (Fink 2000), we used the immunohistochemical expression of PR in gonadotropes to classify them as activated (with PR expression) or hypertrophied (without PR expression).. In the rat, the presence of PR in gonadotropes is an absolute ...
Conference Call Ligand management will host a conference call today beginning at 4:30 p.m. Eastern time (1:30 p.m. Pacific time) to discuss this announcement and answer questions. To participate via telephone, please dial (877) 407-4019 from the U.S. or (201) 689-8337 from outside the U.S., using the passcode "Ligand." A replay of the call will be available until June 4, 2010 at 5:30 p.m. Eastern time by dialing (877) 660-6853 from the U.S. or (201) 612-7415 from outside the U.S. The account number is 361 and the passcode is 349820. Individual investors can access the Webcast through Ligands web site at www.ligand.com. Ligand Analyst Day Ligand will hold an Analyst Day event on June 24, 2010 in New York City. Ligand will announce full details regarding the event including program agenda by the end of May. Additional event details and webcast information will be posted closer to the event on Ligands investor Web site at www.ligand.com. About Ligand Pharmaceuticals Ligand discovers and develops ...
5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-iodo-A-85380) and labeled it with 125I and123I. Here we present the results of experiments characterizing this radioiodinated ligand in vitro. The affinity of 5-[125I]iodo-A-85380 for α4β2 nAChRs in rat and human brain is defined by K d values of 10 and 12 pM, respectively, similar to that of epibatidine (8 pM). In contrast to epibatidine, however, 5-iodo-A-85380 is more selective in binding to the α4β2 subtype than to other nAChR subtypes. In rat adrenal glands, 5-iodo-A-85380 binds to nAChRs containing α3 and β4 subunits with 1/1000th the affinity of epibatidine, and exhibits 1/60th and 1/190th the affinity of epibatidine at α7 and muscle-type nAChRs, respectively. Moreover, unlike epibatidine and cytisine, 5-[125I]iodo-A-85380 shows no binding in any brain regions in mice homozygous for a mutation in the β2 subunit of nAChRs. Binding of 5-[125I]iodo-A-85380 in rat brain is reversible, and is characterized by high specificity and a slow rate ...
Kevin Pfleger (University of Western Australia) talks about his experience with BRET-based ligand binding on BMG LABTECH Microplate readers. Watch here.
OPUS (Open Publications of UTS Scholars) is the UTS institutional repository. It showcases the research of UTS staff and postgraduate students to a global audience. For you, as a researcher, OPUS increases the visibility and accessibility of your research by making it openly available regardless of where you choose to publish.. Items in OPUS are enhanced with high quality metadata and seeded to search engines such as Google Scholar as well as being linked to your UTS research profile, increasing discoverability and opportunities for citation of your work and collaboration. In addition, works in OPUS are preserved for long-term access and discovery.. The UTS Open Access Policy requires UTS research outputs to be openly available via OPUS. Depositing your work in OPUS also assists you in complying with ARC, NHMRC and other funder Open Access policies. Providing Open Access to your research outputs through OPUS not only ensures you comply with these important policies, but increases opportunities ...
The hematopoietic compartment is one of the most severely damaged after chemotherapy, radiotherapy or accidental irradiations. Whatever its origin, the resulting damage to the bone marrow remains difficult to evaluate. Thus, it would be of great interest to get a biological indicator of residual hematopoiesis in order to adapt the treatment to each clinical situation. Recent results indicated that the plasma Flt3 ligand concentration was increased in patients suffering from either acquired or induced aplasia, suggesting that Flt3 ligand might be useful as a biological indicator of bone marrow status. We thus followed in a mouse model as well as in several clinical situations the variations in plasma Flt3 ligand concentration, after either homogeneous or heterogeneous irradiations. These variations were correlated to the number of hematopoietic progenitors and to other parameters such as duration and depth of pancytopenia ...
diss/z2006/0801 Prediction of protonation states in ligand-protein complexes upon ligand binding Recent hardware development increase the computing power, in consequence many biological and chemical processes can now be successfully modelled in a way which was not to imagine 20 years ago. Examples of such processes are molecular dynamics studies of large biomolecules, the prediction of free energy of binding for protein-ligand complexes, investigations of reaction paths in enzymes, to mention only a few. One issue which is still unresolved concerns the accurate estimation of protonation states in protein-ligand complexes. In this thesis, we present the development of a novel charge assignment procedure named PEOE_PB (Partial Equalisation of Orbital Electronegativities - optimized for Poisson-Boltzmann calculations), which represents a method for the assignment of atomic partial charges. It works reliably with both proteins and small organic molecules using a consistent approach. Such charges are ...
Title:Class A GPCRs: Structure, Function, Modeling and Structure-based Ligand Design. VOLUME: 23 ISSUE: 29. Author(s):Xiaojing Cong*, Jeremie Topin and Jerome Golebiowski*. Affiliation:Institute of Chemistry - Nice, UMR 7272 CNRS - University Nice - Sophia Antipolis, 06108 Nice cedex 2, Institute of Chemistry - Nice, UMR 7272 CNRS - University Nice - Sophia Antipolis, 06108 Nice Cedex 2, Institute of Chemistry - Nice, UMR 7272 CNRS - University Nice - Sophia Antipolis, 06108 Nice cedex 2. Keywords:GPCR, ligand design, allosteric modulation, ligand bias, homology modeling, molecular dynamics.. Abstract:G protein-coupled receptors (GPCRs), especially the class A, are the most heavily investigated drug targets in the pharmaceutical industry. Tremendous efforts have been made by both industry and academia to understand the molecular structure and function of this large family of transmembrane proteins. Our understanding in GPCR activation has evolved from the classical inactive-active two-state ...
Our study demonstrates for the first time that treatment with RTL after onset of MCAO reduces cortical and total infarct size, inhibits infiltrating inflammatory cells, particularly activated macrophages/microglial cells and DCs, into postischemic brain, and partially preserves spleen cell numbers that are typically ablated after MCAO. This result was specific to RTL551 treatment in C57BL/6 male mice and verified using a "humanized" RTL1000 construct to treat MCAO in HLA-DR2-Tg mice. The results clearly show that the therapeutic activity of RTL requires a neuroantigen peptide (mouse or human MOG-35-55) tethered to an MHC moiety that closely matches the Class II of the treated mouse strain (I-Ab for C57BL/6 mice and HLA-DR2 for DR2-Tg mice). In contrast, treatment of C57BL/6 mice with RTL553 comprised of I-Ab coupled to I-Ea-52-68 (a nonneuroantigen peptide) and RTL342M comprised of HLA-DR2 (nonmatched MHC Class II) coupled to mMOG-35-55 peptide did not have therapeutic effects.. Beyond the ...
Tyrosine phosphorylation plays a critical role in the control of many cellular processes including cell proliferation, differentiation, metabolism, as well as cell survival and migration. Receptor tyrosine kinases undergo ligand dependent dimerization which activates their intrinsic protein tyrosine kinase (PTK) domains. We have determined the crystal structure of Stem cell factor (SCF) and fibroblast growth factor (FGF), two ligands of receptor tyrosine kinases. In addition, we have determined the crystal structure of FGF in complex with the extracellular ligand binding domain of FGF-receptor (FGFR) and with a heparin sulfate oligosacchride. The structure of the ternary FGF/heparin/FGFR complex provides a molecular view of how FGF acts in concert with heparin to induce the dimerization and activation of FGF-receptors. We have also determined the crystal structure of the catalytic PTK domain of FGFR in complex with an ATP analogue or in complex with specific PTK inhibitors of FGFR activity and ...
It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK ...
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The goal of our ligand-centric approach is to facilitate discovery of protein function by providing detailed information about ligand binding sites and ligand-specific binding motifs, aiding in structure-based modeling efforts and helping crystallographers identify unexpected molecular commonalities and similarities with other protein-ligand systems.. Carrying out comparative analysis on binding sites of similar ligands yields valuable information about conserved and non-conserved interactions. While the conserved interactions are determinants of ligand affinity, the non-conserved interactions govern the specificity. For example, similarities between the ligand binding sites of an odorant receptor and metabotropic glutamate receptors defined the motif for ligand recognition in the G-protein coupled receptor superfamily [52]. Our ligand conformational and classification analysis will aid in choosing the right conformation of the ligand for docking studies. For example, if only an unbound ...
An increasing number of therapeutic antibodies targeting tumors that express the epidermal growth factor receptor (EGFR) are in clinical use or late stages of clinical development. Here we investigate the molecular basis for inhibition of EGFR activation by the therapeutic antibody matuzumab (EMD72000). We describe the X-ray crystal structure of the Fab fragment of matuzumab (Fab72000) in complex with isolated domain III from the extracellular region of EGFR. Fab72000 interacts with an epitope on EGFR that is distinct from the ligand-binding region on domain III and from the cetuximab/Erbitux epitope. Matuzumab blocks ligand-induced receptor activation indirectly by sterically preventing the domain rearrangement and local conformational changes that must occur for high-affinity ligand binding and receptor dimerization. Matuzumab binding to EGFR prevents the conformational rearrangement required for dimerization.,Schmiedel J, Blaukat A, Li S, Knochel T, Ferguson KM Cancer Cell. 2008 ...
The Notch receptor is part of a core signalling pathway which is highly conserved in all metazoan species. It is required for various cell fate decisions at multiple stages of development and in the adult organism, with dysregulation of the pathway associated with genetic and acquired diseases including cancer. Although cellular and in vivo studies have provided considerable insight into the downstream consequences of Notch signalling, relatively little is known about the molecular basis of the receptor/ligand interaction and initial stages of activation. Recent advances in structure determination of the extracellular regions of human Notch-1 and one of its ligands Jagged-1 have given new insights into docking events occurring at the cell surface which may facilitate the development of new highly specific therapies. We review the structural data available for receptor and ligands and identify the challenges ahead.
Neurodegenerative diseases feature neurochemical and neuropathological changes which are intimately linked with excitotoxicity. PSD-95 a post-synaptic scaffold protein of the NMDA receptor complex, containing PDZ domains coupling to a PMCa2B calcium channel, NMDAR2, and i-nos, has been found to mediate Glutamate induced excitotoxicity. Neuronal damage may be mediated by calcium intrusion and oxidative stress and PSD-95 is a potential therapeutic target. PDZ binding ligands have been designed based on the C-terminal sequence of the PMCa2b calcium channel sub-unit in order to disrupt its interaction with PSD95 via PDZ domain 1. Current PDZ binding ligands currently have Kd constants in the micromolar range and tighter binding is required (Kd constants in nanomolar range) for therapeutic use. Structural alterations have been proposed by various researchers to this end including cyclisation of PDZ peptide ligands. Putative PDZ binding ligands were modeled in Silico based on existing structures but ...
Chemical Thermodynamics of Compounds and Complexes of U, Np, Pu, Am, Tc, Se, Ni and Zr With Selected Organic Ligands Physics Science Ebook by Wolfgang Hummel, Federico J. Mompean, Myriam IllemassèNe, Myriam Illemassne,
Serotonin or 5-hydroxytryptamine subtype 2C (5-HT2C) receptor belongs to class A amine subfamily of Gprotein- coupled receptor (GPCR) super family and its ligands has therapeutic promise as anti-depressant and -obesity agents. So far, bovine rhodopsin from class A opsin subfamily was the mostly used X-ray crystal template to model this receptor. Here, we explained homology model using beta 2 adrenergic receptor (β2AR), the model was energetically minimized and validated by flexible ligand docking with known agonists and antagonists. In the active site Asp134, Ser138 of transmembrane 3 (TM3), Arg195 of extracellular loop 2 (ECL2) and Tyr358 of TM7 were found as important residues to interact with agonists. In addition to these, V208 of ECL2 and N351 of TM7 was found to interact with antagonists. Several conserved residues including Trp324, Phe327 and Phe328 were also found to contribute hydrophobic interaction. The predicted ligand binding mode is in good agreement with published mutagenesis and ...
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4. Protein Tyrosine Kinase (PTK) family; Fibroblast Growth Factor Receptor 4 (FGFR4); catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FGFR4 is part of the FGFR subfamily, which are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of ...
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2. Protein Tyrosine Kinase (PTK) family; Fibroblast Growth Factor Receptor 2 (FGFR2); catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FGFR2 is part of the FGFR subfamily, which are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of ...
This is a pretty good hit rate. Generally virtual screening campaigns are lucky to have a hit rate of a few percent. Curiously, the authors also found a similarly high hit rate during a past VS campaign against the well-known β2 adrenergic receptor. What could be responsible for this high hit rate against GPCRs? The reasons are interesting. One reason could be that GPCRs are very well adapted to bind small molecules in compact pockets, enclosing them and forming many kinds of productive interactions. But more intriguingly, as the authors have noted earlier, there is "biogenic bias" in favor of certain target-specific chemotypes in commercial libraries that are screened, both during VS as well as HTS. This in turn reflects the biases of medicinal chemists in picking and synthesizing certain kinds of chemotypes based on the importance of drug targets and past successes in hitting these targets. GPCRs clearly are enormously important, and GPCR-friendly ligand chemotypes thus constitute a large ...
The components consist of solvent effects, conformational changes in the protein and ligand, free energy due to protein-ligand interactions, internal rotations, association energy of ligand and receptor to form a single complex and free energy due to changes in vibrational modes.[24] A low (negative) energy indicates a stable system and thus a likely binding interaction. An alternative approach is to derive a knowledge-based statistical potential for interactions from a large database of protein-ligand complexes, such as the Protein Data Bank, and evaluate the fit of the pose according to this inferred potential. There are a large number of structures from X-ray crystallography for complexes between proteins and high affinity ligands, but comparatively fewer for low affinity ligands as the later complexes tend to be less stable and therefore more difficult to crystallize. Scoring functions trained with this data can dock high affinity ligands correctly, but they will also give plausible docked ...
The modification of medical device surface with adhesive ligands has been recently shown to be an effective means for making a bioselective surface which can inhibit bacterial adhesion while promoting host cell adhesion on device materials. Currently, the lack of quantitative correlation between the adhesion strength of bacteria, nature of adhesive ligand and adhesion kinetics of mammalian cells hinders the development of such device surface. In this study, the biophysical responses of bacteria and mammalian cells towards adhesive ligand on model device surfaces formed by the chemisorption of dopamine (a moderate antibiotic) on glass are elucidated. The effects of RGD, collagen and dopamine modification on the adhesion strength of two clinically significant bacteria including Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were investigated by the determination of minimum lateral forces for bacterial detachment and the density of adhering bacteria. The result indicates that RGD ...
Factors that govern specificity-promiscuity will be examined using an ensemble of ligand-receptor systems that span a specificity-affinity continuum. Through the comparative analyses of the structurally homologous protein-ligand pairs, factors that influence specificity will be illuminated as enhancing features will become enriched and diminishing ones will be "washed away," thus providing deeper understanding of how the structural properties of ligand pockets relates to ligand-binding properties. The ensemble will be derived from the BmrR transcription factor, which recognizes numerous structurally unrelated cationic lipophilic ligands and regulates the expression of a multidrug efflux pump. A convergent molecular library will be generated using phage display and biopanning selective pressures designed to enforce increases in binding specificity and affinity. The binding properties of the variants will be characterized using thermodynamic, kinetic, and structural methods. Some specific issues ...
The mechanism by which low affinity adhesion molecules function to produce stable cell-cell adhesion is unknown. In solution, the interaction of human CD2 with its ligand CD58 is of low affinity (500 mM-1) and the interaction of rat CD2 with its ligand CD48 is of still lower affinity (40 mM-1). At the molecular level, however, the two systems are likely to be topologically identical. Fluorescently labeled glycosylphosphatidylinositol-anchored CD48 and CD58 were prepared and incorporated into supported phospholipid bilayers, in which the ligands were capable of free lateral diffusion. Quantitative fluorescence imaging was used to study the binding of cell surface human and rat CD2 molecules to the fluorescent ligands in contact areas between Jurkat cells and the bilayers. These studies provide two major conclusions. First, CD2/ligand interactions cooperate to align membranes with nanometer precision leading to a physiologically effective two-dimensional affinity. This process does not require the intact
Denticity (represented by κ) refers to the number of times a ligand bonds to a metal through noncontiguous donor sites. Many ligands are capable of binding metal ions through multiple sites, usually because the ligands have lone pairs on more than one atom. Ligands that bind via more than one atom are often termed chelating. A ligand that binds through two sites is classified as bidentate, and three sites as tridentate. The "bite angle" refers to the angle between the two bonds of a bidentate chelate. Chelating ligands are commonly formed by linking donor groups via organic linkers. A classic bidentate ligand is ethylenediamine, which is derived by the linking of two ammonia groups with an ethylene (−CH2CH2−) linker. A classic example of a polydentate ligand is the hexadentate chelating agent EDTA, which is able to bond through six sites, completely surrounding some metals. The number of times a polydentate ligand binds to a metal centre is symbolized by "κn", where n indicates the number ...