Journal of Pharmacology and Experimental Therapeutics May 31, 2019, jpet.119.257071; DOI: https://doi.org/10.1124/jpet.119.257071 ...
Structure of arterolane(1) and arterolane-inspiredtrioxolane-drug conjugate 2. Free drug is releasedfrom 2 in the presence of ferrous iron.
TY - JOUR. T1 - A Bisamide Derivative of [Mn(1,4-DO2A)] - Solution Thermodynamic, Kinetic, and NMR Relaxometric Studies. AU - Forgács, Attila. AU - Tei, Lorenzo. AU - Baranyai, Z.. AU - Tóth, Imre. AU - Zékány, László. AU - Botta, Mauro. PY - 2016/3/1. Y1 - 2016/3/1. N2 - A new 1,4-DO2A-bisamide [1,4-DO2AM; 1,4-DO2A = 2,2′-(1,4,7,10-tetraazacyclododecane-1,4-diyl)diacetic acid] ligand was synthesized, and its MnII complex was prepared and investigated in detail by solution thermodynamic, kinetic, and 1H and 17O NMR relaxometric measurements. Although the stability constant of [Mn(1,4-DO2AM)]2+ (log KMnL = 12.64) is 2.5 log K units lower than that of [Mn(1,4-DO2A)], its kinetic inertness, investigated through its transmetallation reactions with Zn2+ ions, is much higher. In particular, the dissociation half-life (t1/2) of [Mn(1,4-DO2AM)]2+ is ten times higher than that of [Mn(1,4-DO2A)] (t1/2 = 556 vs. 49 h, pH 7.4). The longer rotational correlation time (τR = 53 ps) for ...
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Molecular imaging is an emerging multidisciplinary field that addresses the visualisation of diseases at the cellular and molecular levels. This thesis focuses on the development of a synthetic Affibody molecule-based imaging tracer for the detection of HER2 expression in malignant tumours.. Papers I-IV report the development of the HER2-specific Affibody molecule, ZHER2:342 by peptide synthesis and the use of different chelators attached to the N-terminus to allow 99mTc-labelling. Paper I described the optimisation of labelling of Affibody molecules using cysteine-based chelator sequences, in which the direct labelling method under alkaline conditions was the most suitable one. Papers II-IV report the development and optimisation of the in vivo properties of the HER2-specific Affibody molecule for high-contrast imaging. By using an array of mercaptoacetyl-based chelators, it was found that the substitution of a single amino acid in a 60 amino acid-long Affibody molecule can dramatically change ...
Radionuclide molecular imaging has the potential to improve cancer treatment by selection of patients for targeted therapy. Affibody molecules are a class of small (7 kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. The NOTA chelator forms stable complexes with a number of radionuclides suitable for SPECT or PET imaging. A maleimidoethylmonoamide NOTA (MMA-NOTA) has been prepared for site-specific labeling of Affibody molecules having a unique C-terminal cysteine. Coupling of the MMA-NOTA to the anti-HER2 Affibody molecule Z(HER2:239S) resulted in a conjugate with an affinity (dissociation constant) to HER2 of 72 pM. Labeling of [MMA-NOTA-Cys(61)]-Z(HER2:239S) with In-111 gave a yield of ,95% after 20 min at 60 degrees C. In vitro cell tests demonstrated specific binding of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) to HER2-expressing cell lines. In mice bearing prostate cancer DU-145 xenografts, the tumor uptake of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) ...
Comparison of 1,4,7,10-tetraazacyclododecane-N,N,N,N-tetraacetic acid (DOTA)-peptide-ChL6, a novel immunoconjugate with catabolizable linker, to 2-iminothiolane-2-p-(bromoacetamido)benzyl-DOTA-ChL6 in breast cancer xenografts. G. L. DeNardo, L. A. Kroger, C. F. Meares, C. M. Richman, Q. Salako, S. Shen, K. R. Lamborn, J. J. Peterson, L. A. Miers, G. R. Zhong, S. J. DeNardo Clinical Cancer Research1998, 4, 2483-90 ...
DOTA 2 uplifts the classic Warcraft 3 Map DOTA into a much higher level graphic-wise. Those who loved DOTA will surely find its second installment much more entertaining compared to its counterparts namely League of Legends and Heroes of Newerth....
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Anti-EGFR Affibody® Molecule Affibody® Molecule datasheet (ab95116). Abcam offers quality products including antibodies, assays and other reagents.
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(1,4,7,10-tetrakis((N-(1H-imidazol-2-yl)carbamoyl)methyl)-1,4,7,10-tetraazacyclododecane)thulium(III): a ParaCEST contrast agent; structure in first source
1-(9-(o-carboxyphenyl)-6-amino-2-chloro-3-xanthanone)-4,10-(diethyl)-7-(2-pyridylmethyl)-1,4,7,10-tetraazacyclododecane: structure in first source
The invention is a chelate of formula I: ##STR1## wherein R1-4 is --CH2 COOH; n is 1 to 5; X is a member selected from the group consisting of --NO2, --NH2, --NCS, --NHCOCH2 --Z, with Z being a member selected from the group consisting of Br and I, --COOH; and --OCH2 OOCH; and M is a metal ion selected from the group of elements consisting of Bi, Pb, Y, Cd, Hg, Al, Th, Sr, and Lanthanides. The invention also includes a chelate, wherein M is a copper ion and n is an integer from 2 to 5. The invention includes chelate conjugates of formula I and ligand conjugates of formula II: ##STR2## The invention also includes methods to use these compounds for treatment of cellular disorders and for diagnostic tests.
Improved bifunctional chelating agents (BFC) are required for copper-64 radiolabelling of monoclonal antibodies (mAbs) under mild conditions to yield stable, target-specific imaging agents. Four different bifunctional chelating agents (BFC) were evaluated for Fab (Fragment antigen binding) conjugation and radiolabelling with copper-64. Two DOTA- (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and two NOTA- (1,4,7-triazacyclononane-1,4,7-triacetic acid) derivatives bearing a p-benzyl-isothiocyanate group were conjugated to Fab-trastuzumab - which targets the HER2/neu receptor - and the average number of chelators attached ranged from 2.4 to 4.3 macrocycles per Fab. Labelling of the immunoconjugate with copper-64 was achieved in high radiochemical yields after 45 min at 37 °C, and the radiochemical purity of each (64)Cu-BFC-Fab-trastuzumab reached 97% after purification. The affinity of each (64)Cu-BFC-Fab-trastuzumab ranged between 10 and 50 nM as evaluated by in vitro saturation assays using
|BR| PURPOSE: To industrially and advantageously produce in short process N-β- hydroxyalkyl-tri-N-carboxylalkyl-1,4,7,10-tetraazacyclododecanes or the like important as an NMR diagnostic. |BR|CONSTITUTION: The intermediate of formula III (R2 is formula IV) is obtained by reacting a compound of formula I (n is 2 or 3) which is obtained from 1,4,7,10- tetraazacyclodecane or 1,4,8,11-tetraazacyclotetradecane with an epoxide of formula II (R4 and R5 are each H or alkyl). A compound of formula VI is obtained by saponifying the resultant intermediate of formula III to form an intermediate of formula V and reacting it with a compound of the formula; X-CH2COOH (X is an eliminable group; Z is H, a metal cation or the like) in the presence of an acid scavenger. Then a metal complex of the compound of formula IV, an inorganic and/or organic base, an amino acid or amino acid amide and their salts are obtained by the reaction of the compound of formula VI with a metal oxide or a metal salt of an element with atomic
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See moreThe synthesis and characterisation of a new dinuclear GdIII-PtII complex (1·PF6) containing a functionalised macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid derivative linked to a PtII-terpy (terpy = 2,2′ : 6′,2″-terpyridine) unit by means of a short thiolato linker are reported. The complex was synthesised in six steps from cyclen by means of a modular synthetic strategy. A preliminary DNA-binding study with calf-thymus DNA (ct-DNA) was performed on 1·PF6 by means of linear dichroism (LD). The observed changes in the DNA LD signal in the presence of the metal complex are fully consistent with an intercalative binding mode. Furthermore, an induced negative LD signal in the ultraviolet absorption region of the complex provides strong evidence of a strong DNA-binding interaction. The in vitro cytotoxicity of 1·PF6 towards a human glioblastoma cell line (T98G) was also determined ...
A new noninvasive radiation-free method to measure gastric emptying in humans was developed. The upper abdomen was recorded with a magnetic resonance imager after administration of a liquid meal containing Gadolinium tetraazacyclododecane tetraacetic acid as a magnetic resonance image (MRI) marker. …
DotA 6.78c LoD Map is now released. Legends of DotA is a modified version of IceFrogs DotA in which you play any hero with your desired skills combination or optionally you can go random. Currently, this map is only compatible with AP, AR SD and MD mode. However, you can enter additional modes for more restrictions/balance. The current version is v6.78c LoD v2g which brings tons of improvements and balance to the skills to avoid misuse ...
DotA 6.78c LoD Map is now released. Legends of DotA is a modified version of IceFrogs DotA in which you play any hero with your desired skills combination or optionally you can go random. Currently, this map is only compatible with AP, AR SD and MD mode. However, you can enter additional modes for more restrictions/balance. The current version is v6.78c LoD v2g which brings tons of improvements and balance to the skills to avoid misuse ...
A process for the preparation of compound of formula (I A), decahydro-2a,4a,6a,8a-tetraazacyclopent[fg]accnaphthylene and the corresponding functionalized compounds of general formula (I), intermediates for the preparation of 1,4,7,10-tetraazacyclododecane (II A) and corresponding derivatives (II), by preparation of compounds of general formula (III) and subsequent reduction thereof. ##STR1##
Two DO3A-based ligands appended with the propylphosphonate side arm and their Ln3+ complexes were investigated. Proton relaxometric in vitro studies at 20 MHz and 60 MHz and 37 °C of the Gd3+ complex containing free acid exhibited relative changes of up to 56% in r1 relaxivity when the pH of the medium was changed from 4 to 7. This change is explained by the decrease in the number of coordinated water molecules from two to one. Temperature-dependent relaxivity and NMRD profiles of Gd3+ complexes showed a fast water exchange and a slightly increased rotational correlation time, which is characteristic of phosphonate-containing compounds. Thermodynamic and kinetic studies of the Gd3+ and Eu3+ complexes were performed by means of potentiometry and luminescence spectroscopy. The results indicate that the thermodynamic stability and kinetic inertness of these complexes are sufficient for their in vivo application. ...
Anti-Insulin Affibody® Molecule Affibody® Molecule datasheet (ab31906). Abcam offers quality products including antibodies, assays and other reagents.
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Bots no longer random their heroes. They will now try to build a somewhat reasonable team comp based on hero role, stuns, and melee/ranged, and do so over the entire hero selection phase ...
Aphotic Shield cast range increased from 350 to 450 Armor reduced from 4 to 2 Base attack time improved from 1.45 to 1.35 The heros attack rate improves the lower the Base Attack Time is, this is a buff. Base HP regeneration increased from 0.25 to 1 Battle Hunger rescaled from 15/17/25/33 to 15...
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