A racemic synthesis of two diastereoisomeric α-benzyloxycarbonylamino substituted trans-fused bicyclic lactams (4 and 5), was achieved from cyclopentene oxide. These lactams are useful intermediates to investigate the possibility of using a trans-lactam template as a replacement for the β-lactam ring found i
Although β-lactam monotherapy may be sufficient in non-critically ill patients with community-acquired pneumonia, the value of combination antibiotic regimens in community-onset neutropenic pneumonia remains unclear. A retrospective cohort study was conducted to compare the effects of combination antibiotic regimens to those of β-lactam monotherapy in cancer patients with community-onset neutropenic pneumonia. Electronic medical records of patients diagnosed with community-onset neutropenic pneumonia between March 1995 and February 2015 at a tertiary care center were reviewed. During the study period, 165 cancer patients with community-onset neutropenic pneumonia were identified. Seventy-two patients received β-lactam monotherapy and 93 received combination therapy (β-lactam plus either a macrolide or fluoroquinolone). Causative pathogens were identified in 27.9% of the patients, and only two were positive for atypical pathogens. Although 30-day mortality was higher in the β-lactam group (15.3%
A beta-lactam (β-lactam) ring is a four-membered lactam. (A lactam is a cyclic amide.) It is named as such because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is 2-azetidinone. The β-lactam ring is part of the core structure of several antibiotic families, the principal ones being the penicillins, cephalosporins, carbapenems, and monobactams, which are, therefore, also called β-lactam antibiotics. Nearly all of these antibiotics work by inhibiting bacterial cell wall biosynthesis. This has a lethal effect on bacteria, although any given bacteria population will typically contain a subgroup that is resistant to β-lactam antibiotics. Bacterial resistance occurs as a result of the expression of one of many genes for the production of β-lactamases, a class of enzymes that break open the β-lactam ring. More than 1,800 different β-lactamase enzymes have been documented in various species of bacteria. These enzymes vary widely in ...
Dithiolopyrrolone antibiotics share a unique disulfide-bridged heterobicyclic core and exhibit potent activities against bacteria, fungi, and mammalian cancer c...
TY - JOUR. T1 - Monocyclic β-lactams loaded on hydroxyapatite: new biomaterials with enhanced antibacterial activity against resistant strains.. AU - Giacomini, Daria. AU - Torricelli, Paola. AU - Gentilomi, G.. AU - Boanini, Elisa. AU - Gazzano, Massimo. AU - Bonvicini, F.. AU - Benetti, E. AU - Soldati, R. AU - Martelli, Giulia. AU - Rubini, K.. AU - Bigi, A.. PY - 2017/6/2. Y1 - 2017/6/2. N2 - The development of biomaterials able to act against a wide range of bacteria, including antibiotic resistant bacteria, is of great importance since bacterial colonization is one of the main causes of implant failure. In this work, we explored the possibility to functionalize hydroxyapatite (HA) nanocrystals with some monocyclic N-thio-substituted β-lactams. To this aim, a series of non-polar azetidinones have been synthesized and characterized. The amount of azetidinones loaded on HA could be properly controlled on changing the polarity of the loading solution and it can reach values up to 17 wt%. ...
TY - JOUR. T1 - Enzyme deactivation due to metal-ion dissociation during turnover of the cobalt-β-lactamase catalyzed hydrolysis of β-lactams. AU - Badarau, Adriana. AU - Page, Michael I.. PY - 2006/9/12. Y1 - 2006/9/12. N2 - Metallo-β-lactamases are native zinc enzymes that catalyze the hydrolysis of β-lactam antibiotics but are also able to function with cobalt (II) and require one or two metal ions for catalytic activity. The kinetics of the hydrolysis of benzylpenicillin catalyzed by cobalt substituted β-lactamase from Bacillus cereus (BcII) are biphasic. The dependence of enzyme activity on pH and metal-ion concentration indicates that only the di-cobalt enzyme is catalytically active. A mono-cobalt enzyme species is formed during the catalytic cycle, which is virtually inactive and requires the association of another cobalt ion for turnover. Two intermediates with different metal to enzyme stoichiometries are formed on a branched reaction pathway. The di-cobalt enzyme intermediate is ...
lactamases are the most widespread resistance mechanism to -lactams and are categorized into four classes, each exhibiting a unique mechanism for destruction of -lactam substrates. Of particular concern are the class D -lactamases, which hydrolyze several of the most potent -lactams in clinical use. In part, resistance derives from the structural similarity of the inhibitors to the -lactams themselves. Therefore an urgent need exists for novel inhibitors that do not resemble -lactams. Research in the Powers lab employs a structure-based approach to identify and characterize binding sites on the class D -lactamases OXA-1 and OXA-24 and will be used to discover novel, non- -lactam inhibitors for these key resistance enzymes using molecular docking.. ...
NAME VERECOLENE CM 5 MG COATED TABLETS PHARMACOTHERAPEUTICCATEGORY Contact laxatives.ACTIVE PRINCIPLESSacodyl 5 mg.EXCIPIENTIC Microcrystalline cellulose, pregelatinised maize starch, talc, glycerol, povidone, methacrylate lactam, lactam, lactam, lactam, lactam, lactam, rubber.
Dosage forms and methods for providing sustained release of reboxetine are provided. The sustained release dosage forms provide therapeutically effective average steady-state plasma reboxetine concentrations when administered once per day. This once-a-day dosing regimen results in only one peak plasma reboxetine concentration occurrence in each 24 hour period. In addition, the peak plasma reboxetine concentration occurs at a later time following dose administration and exhibits a lesser magnitude than the peak plasma reboxetine concentration that occurs following administration of reboxetine in an immediate-release dosage form.
A monocyclic ring in their structure characterizes monobactams, a subclass of β-lactam antibiotics. Many of these compounds have a bactericidal mechanism of ac
A versatile and highly stereoselective synthetic route to functionalized bi- and tricyclic lactams (up to , 20:1 dr and 99% ee) in one pot from simple starting materials (allylic alcohols, enals, diamines and amino alcohols) using cascade transformations promoted by chiral amine/BrOnsted or metal/chiral amine/BrOnsted relay catalysis is disclosed. Here molecular oxygen is employed as the terminal oxidant for the latter relay catalysis approach.. ...
Production of chromosome-encoded β-lactamases confers resistance to β-lactams in many Gram-negative bacteria. Some inducible β-lactamases, especially the class C β-lactamase AmpC in Enterobacteriaceae, share a common regulatory mechanism, the ampR-ampC paradigm. Induction of ampC is intimately linked to peptidoglycan recycling, and the LysR-type transcriptional regulator AmpR plays a central role in the process. However, our previous studies have demonstrated that the expression of class D β-lactamase gene blaA in Shewanella oneidensis is distinct from the established paradigm since an AmpR homolog is absent and major peptidoglycan recycling enzymes play opposite roles in β-lactamase expression ...
The asymmetric synthesis of monocyclic β-lactams belong to five categories: a) asymmetric induction from the imine component; b) asymmetric induction from the ketene component; c) double stereodifferentiating cycloadditions; d) carbacephem intermediates and e) 2-oxaisocephems and 2-isocephems.[...]
The diastereoselective synthesis of fluorinated δ-lactams has been achieved through an efficient five step process. The route can tolerate a range of functionalities, and provides a quick route for the generation of new fluorinated medicinal building blocks. ...
3-hydroxy-13-amino-13,17-secoandrostan-17-oic-13,17-lactam p-bis(2-chloroethyl)amino phenyl acetate: an alkylating agent for treating breast cancer; lactandrate is the (5alpha)-isomer; structure in first source
title: Novel Lactam Type Pyridine Derivatives Improves Myocardium Dysfunction Derived from Ischemic Injury, doi: none, category: Article
A lactam or cyclic amide is an amide in the molecule of which there are one or two carbon chains connecting the carbonyl carbon to the nitrogen atom.. eg:. ...
Faropenem is the only oral penem antibiotic currently available & it is a hybrid compound that exhibit similarities to both penicillin & cephalosporin. Faropenem is an attractive treatment option for community acquired infections & can be used as an empirical therapy. It is the modern and promising approach to rationalize use of antimicrobials in hospital. Can be used as step down therapy for carbapenem and cephalosporin. ...
The discovery of novel β-lactamases and penicillin-binding proteins (PBPs) often requires kinetic characterization. As such, the rate at which a β-lactamase hydrolyzes a β-lactam is influenced by several factors. The first is concentration of β-lactam, which is designated [S] and is expressed in units of molarity. The second is temperature. As the temperature rises, molecular motion, and hence collisions between β-lactamase and β-lactam, and the rates of interconversion of intermediates increase. The third factor is the presence of inhibitors. β-lactamase inhibitors are clinically used to hinder the activity of the β-lactamase. The last is pH: the charge of active-site groups and the conformation of a protein are influenced by pH, and enzyme activity is crucially dependent on both these factors. The equations of enzyme kinetics are conceptual tools that allow us to interpret quantitative measurements of enzyme activity. Nitrocefin is the most practical reference compound, since the accumulation
This report on danoprevir clearly shows it is a potent, pan-genotypic, macrocyclic second-generation PI that meets all of these criteria. However, the grade 4 elevations in alanine aminotransferase (ALT) levels seen in 2% of danoprevir-treated patients (including three in the 900-mg cohort and one in the 600-mg cohort) that were seen in this study became a major roadblock to the phase III development of the compound. Instead, the coadministration of low-dose ritonavir, another protease inhibitor, which significantly inhibits danoprevir reactive metabolite formation, has allowed the compound to move forward into advanced studies without the hepatotoxicity concern [J. Hepatol. 2012;56(Suppl 2):S467; Hepatology 2012;56(Suppl 1):552A; Hepatology 2012;56(Suppl 1):231A; J. Hepatol. 2012;56(Suppl 2):S555 ...
A review of Beta-Lactam antibiotics in infectious diseases practice.. Stay in touch! Download our app in the iTunes store or the Google Marketplace.. ...
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. ...
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. ...
ChapterInfo , title=The Synthesis of β-Lactams , authors=Sheehan, John C.; Corey, Elias J. , year = [[Year Published::1957]] , volume=[[Volume::9]], doi=10.1002/0471264180.or009.06 , wikiarticle=Unknown , wparticle=β-lactam }} {{#set:Author=Sheehan, John C.; Corey, Elias J.}} [[Category:Full Organic Reactions chapters]] {{#set:DOI=10.1002/0471264180.or009.06 ...
A major challenge in treating patients is the selection of the "right" antibiotic regimen. Given that the optimal β-lactam-β-lactamase inhibitor pair is dependent upon the spectrum of β-lactamase enzymes produced and the frequency of resistance to the β-lactamase inhibitor, it might be useful if a stand-alone were available for the clinician to pair with the "right" β-lactam rather than only in a fixed combination. In this communication, we describe a one-compartment in vitro infection model studies conducted to identify the magnitude of the pharmacokinetic-pharmacodynamic (PK-PD) index for a β-lactamase inhibitor, CB-618, that would restore the activity of four β-lactam partner agents (cefepime, ceftazidime, ceftolozane, and meropenem) with varying dose (1 or 2 g) and dosing intervals (8 or 12 h ...
Mignon A. Keaton, Roberto R. Rosato, Konrad B. Plata, Christopher R. Singh, Adriana E. Rosato. PLoS One. 2013; 8(8): e71025. Published online 2013 August 5. doi: 10.1371/journal.pone.0071025. PMCID: PMC3733780 ...
Scientifically proven SlimPaws, from Vetality pet products, is a once-a-day soft chew that naturally helps reduce body fat, improve metabolism, and decrease conversion of food to fat. Made in the USA. 30 count.
Actos (Pioglitazone) is a once-a-day prescription pill for type 2 diabetes that along with healthy eating and physical activity helps your body more effectively use its own natural insulin or the... ...
Thanks for your post and nice words. The once-a-day triple combo pill that you allude to (tenfovir/FTC/efavirenz) will likely be commercially available in the near future- perhaps just a month...
Carbapenam synthetase (CarA) is an ATP/Mg2+-dependent enzyme that catalyzes formation of the β-lactam ring in (5R)-carbapenem-3… Expand ...
SWISS-MODEL Template Library (SMTL) entry for 1jwt.1. CRYSTAL STRUCTURE OF THROMBIN IN COMPLEX WITH A NOVEL BICYCLIC LACTAM INHIBITOR
A meta-analysis was performed to investigate whether a switch from β-lactams to glycopeptides for cardiac surgery prophylaxis should be advised. Results of 7 randomized trials (5761 procedures) that compared surgical site infections (SSIs) in subjects receiving glycopeptide prophylaxis with SSIs in those who received β-lactam prophylaxis were pooled. Neither agent proved to be superior for prevention of the primary outcome, occurrence of SSI at 30 days (risk ratio [RR], 1.14; 95% confidence interval [CI], 0.91-1.42). In subanalyses, β-lactams were superior to glycopeptides for prevention of chest SSIs (RR, 1.47; 95% CI, 1.11-1.95) and approached superiority for prevention of deep-chest SSIs (RR, 1.33; 95% CI, 0.91-1.94) and SSIs caused by gram-positive bacteria (RR, 1.36; 95% CI, 0.98-1.91). Glycopeptides approached superiority to β-lactams for prevention of leg SSIs (RR, 0.77; 95% CI, 0.58-1.01) and were superior for prevention of SSIs caused by methicillin-resistant gram-positive bacteria ...
see article for more reactions. Abstract. An oxidative relay Heck arylation reaction enables the construction of chiral α,β-unsaturated δ-lactams, widely used as pharmacophores, in high yields and excellent enantioselectivities. This strategy also allows facile access to 7-substituted α,β-unsaturated ε-lactam products and δ-lactams.. ...
TY - JOUR. T1 - Attributable sources of community-acquired carriage of Escherichia coli containing β-lactam antibiotic resistance genes. T2 - a population-based modelling study. AU - ESBL Attribution Consortium. AU - Mughini-Gras, Lapo. AU - Dorado-García, Alejandro. AU - van Duijkeren, Engeline. AU - van den Bunt, Gerrita. AU - Dierikx, Cindy M.. AU - Bonten, Marc J.M.. AU - Bootsma, Martin C.J.. AU - Schmitt, Heike. AU - Hald, Tine. AU - Evers, Eric G.. AU - de Koeijer, Aline. AU - van Pelt, Wilfrid. AU - Franz, Eelco. AU - Mevius, Dik J.. AU - Heederik, Dick J.J.. PY - 2019. Y1 - 2019. N2 - Background: Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC), plasmid-mediated AmpC-producing E coli (pAmpC-EC), and other bacteria are resistant to important β-lactam antibiotics. ESBL-EC and pAmpC-EC are increasingly reported in animals, food, the environment, and community-acquired and health-care-associated human infections. These infections are usually preceded by asymptomatic ...
An increase in the copper pool in body fluids has been related to a number of pathological conditions, including infections. Copper ions may affect antibiotics via the formation of coordination bonds and/or redox reactions. Herein, we analyzed the interactions of Cu2+ with eight β-lactam antibiotics using UV-Vis spectrophotometry, EPR spectroscopy, and electrochemical methods. Penicillin G did not show any detectable interactions with Cu2+. Ampicillin, amoxicillin and cephalexin formed stable colored complexes with octahedral coordination environment of Cu2+ with tetragonal distortion, and primary amine group as the site of coordinate bond formation. These β-lactams increased the solubility of Cu2+ in the phosphate buffer. Ceftazidime and Cu2+ formed a complex with a similar geometry and gave rise to an organic radical. Ceftriaxone-Cu2+ complex appears to exhibit different geometry. All complexes showed 1:1 stoichiometry. Cefaclor reduced Cu2+ to Cu1+ that further reacted with molecula...r ...
Growth of E. coli at pH 5 protected the bacteria against the lytic effect of beta lactam antibiotics typically observed when the cells are grown at pH 7 or 7.5, i.e., the pH values routinely used in laboratory experiments. In contrast, the typical effects of beta lactam antibiotics on cellular shape and elongation and cell division appeared to be similar in cultures grown under neutral and acid pH conditions. The pH-dependent antibiotic tolerance can also be demonstrated with pneumococci, staphylococci, streptococci, and Bacillus subtilis. We suggest that the mechanism of the pH-dependent antibiotic tolerance may involve either the production of a more stable plasma membrane or the suppression of the activity of a murein hydrolase(s) that catalyzes the antibiotic-induced lysis; at least a fraction of these enzyme molecules may be localized at the cell surface and be accessible to experimental manipulation.. ...
A novel method for the synthesis of α,α-difluoro-γ-lactam derivatives has been developed using a copper/amine catalyst via a tandem radical cyclization pathway. This protocol provides a convenient and straightforward strategy for the rapid construction of various 3,3-difluoro-γ-lactam moieties from easily av
The Schmidt reaction is an organic reaction in which an azide reacts with a carbonyl group to give an amine or amide, with expulsion of nitrogen. It is named after Karl Friedrich Schmidt (1887-1971), who first reported it in 1924 by successfully converting benzophenone and hydrazoic acid to benzanilide. Surprisingly, the intramolecular reaction wasnt reported until 1991 but has become important in the synthesis of natural products The carboxylic acid Schmidt reaction starts with acylium ion 1 obtained from protonation and loss of water. Reaction with hydrazoic acid forms the protonated azido ketone 2, which goes through a rearrangement reaction with the alkyl group R, migrating over the C-N bond with expulsion of nitrogen. The protonated isocyanate is attacked by water forming carbamate 4, which after deprotonation loses carbon dioxide to the amine. The reaction is related to the Curtius rearrangement except that in this reaction the azide is protonated and hence with different intermediates. ...
CA-MRSA isolates s were initially associated with lethal infections in children in the Midwest (21). CA-MRSA strains have since become the most frequent cause of skin and soft tissue infections in emergency rooms in the United States, increasing in frequency from 29% in 2001 to 2002 to 64% in 2003 to 2004 (32, 43, 44). However, the epidemiology of MRSA disease is changing, with the pulsed-field type USA300 now being the most common strain in the community but also emerging as a major cause of nosocomial bloodstream and prosthetic joint infections (33, 52). These epidemiological data underline the need to study the molecular mechanisms of virulence and drug resistance in this strain. PBP4, although not essential for viability, has been associated with low-level resistance to vancomycin and β-lactam antibiotics in HA-MRSA strain COL (11, 22, 24, 30, 45, 53). However, a mutation in pbp4, but not pbp3, in MW2 and USA300 strains has led to a significant decrease in high-level resistance to the ...
Dechra Cefpoderm (cefpodoxime proxetil) is a once-a-day cephalosporin antibiotic for the treatment of skin infections, wounds,and abscesses in dogs caused by susceptible strains of Staphylococcus, Streptococcus, Escherichia coli, Pasteurella and Proteus.
Lilly ICOS - a joint venture between ICOS Corp and Eli Lilly - has filed 2.5mg and 5mg once-a-day versions of the billion-dollar erectile dysfunction drug Cialis with European regulators. - News - PharmaTimes
Darcie Long, a fourth-year in the Chemistry-Biology Interface Program and one of the authors of this study, explained that while most of the clinically relevant β-lactam antibiotics have two fused structures, a different class, called moncyclic antibiotics, only has one ring structure.. Although most antibiotics are bicyclic, Long says the monocyclic antibiotics are "of increasing interest because of their relative resistance to metalloproteases and β-lactamases, which are enzymes involved in conferring antibiotic resistance to some pathogenic bacteria.". Therefore, to better understand this single-ring class of antibiotics, the authors investigated the ring formation in one specific family: norcardicin.. Long and lead author Nicole Gaudelli worked together on all of the benchwork that led to the discovery of the mechanism. They found how the nonribosomal peptide synthetases (NRPSs) were able to create a ring structure in the norcardicin family. Intriguingly, this enzyme has been identified in ...
Medicef Pharma is a leading Pharma Manufacturers in India and one of the biggest EU GMP Certified Beta Lactam Antibiotics Manufacturers. We always focused on developing superior quality products at fair prices to cater to those needs.
Due to widespread resistance to penicillin, the current treatment of choice for S. aureus infections is semi-synthetic penicillin molecules. This resistance is due to the activity of the enzyme penicillinase, which cleaves the β-lactam ring of the penicillin molecule. Penicillinase-resistant β-lactam antibiotics include methicillin, oxacillin, and flucoxacillin. S. aureus strains that have acquired resistance to methicillin have an altered penicillin-binding protein (PBP2a) that has lower affinity for binding β-lactam antibiotics, thus rendering them ineffective. Strains that have acquired this resistance are referred to as methicillin-resistant S. aureus (MRSA). The current gold standard for treatment of MRSA is vancomycin. However, vancomycin is far from ideal due to poor tissue penetration, slow bactericidal activity, and a number of side effects (Gould, 2008). Additional antibiotics utilized include teicoplanin, tegecyline, linezolid, daptomycin, and televancin. Each of those medications ...
have discovered a novel mechanism of resistance to ?-lactams that is independent of penicillinase and the low affinity penicillin bindin protein (PBP), PBP2a, the two known mechanisms of ?-lactam resistance in Staphylococcus aureus. This new type of resistance was identified during experiments in which methicillin- susceptible S. aureus strains were passaged in the presence of each of the two so-called "fifth generation" anti-MRSA cephalosporins, ceftobiprole and ceftaroline. Whole genome sequencing of a ceftobiprole- passage mutant revealed mutations in genes encoding PBP4, a non-essential, low-molecular weight PBP; GdpP, a putative signaling protein; and AcrB, a putative transporter. Ceftaroline also selected for PBP4 and GdpP mutants, but not AcrB mutants, indicating the primary importance of the former two proteins. We hypothesize 1) that a gain of transpeptidase function by mutant PBP4 accounts for high-level ?-lactam resistance; and 2) that GdpP contributes to resistance via a signaling ...
Background -lactam level of resistance in Gram-negative bacteria is a substantial clinical issue in the grouped community, long-term care services, and hospitals. fast and accurate approach to visualizing the SHV category of enzymes in medical examples including Gram-negative bacilli utilizing a fluorescein-labeled polyclonal antibody. Background Level of resistance to -lactam antibiotics in Gram-negative bacterias can be a Volasertib substantial medical issue in the grouped community, long-term treatment, and hospital configurations [1-3]. In the normal Gram-negative bacterias that are in charge of most medical infections, -lactam level of resistance results from creation of penicillinases (mainly the -lactamases specified TEM-1 and SHV-1), cephalosporinases (e.g., extended-spectrum -lactamases, ESBL, of TEM-, SHV- and CTX-M-types), as well as the plasmid or chromosomally encoded AmpC enzymes [1]. Hence, an intense search for book therapeutic real estate agents and fast, accurate detection ...
Poster (2012, April 18). The widespread use of beta-lactam antibiotics has lead to the worldwide appearance of drug-resistant strains. Bacteria have developed resistance to beta-lactams by three main mechanisms: the production of ... [more ▼]. The widespread use of beta-lactam antibiotics has lead to the worldwide appearance of drug-resistant strains. Bacteria have developed resistance to beta-lactams by three main mechanisms: the production of beta-lactamases that catalyze hydrolysis of beta-lactams, the production of low-affinity, drug resistant Penicillin Binding Proteins (PBPs) and the over expression of resistant PBPs. PBPs are interesting targets because they catalyse the last steps of the biosynthesis of peptidoglycan, which is unique in bacteria and has no mammalian analogs, outside the cytoplasmic membrane. Various non-ß-lactam inhibitors of PBPs have been developed with the objective of attempting to stall the development of ß-lactam resistance. Boronic acids are potent ...
Poster (2012, April 18). The widespread use of beta-lactam antibiotics has lead to the worldwide appearance of drug-resistant strains. Bacteria have developed resistance to beta-lactams by three main mechanisms: the production of ... [more ▼]. The widespread use of beta-lactam antibiotics has lead to the worldwide appearance of drug-resistant strains. Bacteria have developed resistance to beta-lactams by three main mechanisms: the production of beta-lactamases that catalyze hydrolysis of beta-lactams, the production of low-affinity, drug resistant Penicillin Binding Proteins (PBPs) and the over expression of resistant PBPs. PBPs are interesting targets because they catalyse the last steps of the biosynthesis of peptidoglycan, which is unique in bacteria and has no mammalian analogs, outside the cytoplasmic membrane. Various non-ß-lactam inhibitors of PBPs have been developed with the objective of attempting to stall the development of ß-lactam resistance. Boronic acids are potent ...
The findings reported here demonstrate that BMS-247550 (EpoB), a lactam analogue of epothilone B, kills cells through a mitochondrial pathway of apoptosis controlled by Bcl-2 and Bax. Similar to Taxol, EpoB causes cell cycle arrest at the G2-M transition and secondarily induces apoptosis of human breast cancer cells. In agreement with this, cells synchronized in G2-M phase of the cell cycle are more sensitive to EpoB-induced cytotoxicity. Upon EpoB treatment, Bax undergoes a conformational change and subsequently translocates to mitochondria. This conformational change of Bax occurs upstream of Bid cleavage, cytochrome c release, and caspase activation. In addition, overexpression of Bcl-2 decreases EpoB-induced Bax conformational change, cytochrome c release, and apoptosis, whereas blockade of Bcl-2 by Bak-BH3 peptide or HA14-1 increases EpoB-mediated cytotoxicity.. In healthy cells, Bax exists predominantly in the cytosol, despite the presence of a typical membrane-anchoring sequence near its ...
4HZO: The Structure of the Bifunctional Acetyltransferase/Decarboxylase LnmK from the Leinamycin Biosynthetic Pathway Revealing Novel Activity for a Double Hot Dog Fold