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Suicide Inhibitor (suicide + inhibitor)

Distribution by Scientific Domains

Chemistry	83%

Selected Abstracts

Multiple Pathways for the Irreversible Inhibition of Steroid Sulfatase with Quinone Methide-Generating Suicide Inhibitors

CHEMBIOCHEM, Issue 9 2009
Vanessa Ahmed
Abstract Unexpected inhibition: 2- and 4-mono- and difluoromethyl estrone sulfate derivatives are suicide inhibitors of steroid sulfatase (STS). Kinetic studies suggest that inhibition by the monofluoro derivatives is a result of a quinone methide intermediate that reacts with active-site nucleophiles, whereas the main inhibition pathway of the 4-difluoromethyl derivative is a result of decomposition of the initial quinone methide to an aldehyde that acts as potent, almost irreversible inhibitor. [source]

Novel synthesis of [1- 11C], -vinyl- , -aminobutyric acid ([1,11C]GVG) for pharmacokinetic studies of addiction treatment

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 3 2002
Zongren Zhang
Abstract , -Vinyl- , -aminobutyric acid (GVG, Vigabatrin®), a suicide inhibitor of GABA-transaminase (GABA-T), has been suggested as a new drug for the treatment of substance abuse. In order to better understand its pharmacokinetics and potential side effects, we have developed a radiosynthesis of carbon-11 (t1/2=20 min) labeled GVG for positron emission tomographic (PET) studies. We report here a novel synthetic strategy to prepare the precursor and to efficiently label GVG with C-11. 5-Bromo-3-(carbobenzyloxy)amino-1-pentene was synthesized in five steps from homoserine lactone, including reduction and methylenation. This was used in a one-pot, two-step radiosynthesis. Displacement of bromide with no-carrier-added [11C]cyanide followed by acid hydrolysis afforded [1- 11C]GVG with decay corrected radiochemical yields of 27±9% (n=6, not optimized) with respect to [11C]cyanide in a synthesis time of 45 min. Copyright © 2002 John Wiley & Sons, Ltd. [source]

A Covalent Chemical Genotype,Phenotype Linkage for in vitro Protein Evolution

CHEMBIOCHEM, Issue 18 2007
Viktor Stein
Display model. Proteins fused to O6 -alkylguanine alkyltransferase (AGT) were expressed in vitro and conjugated to their coding DNA via O6 -benzylguanine, a suicide inhibitor of AGT. The potential of this display system is demonstrated for several proteins in model selection experiments. Enrichments of up to 100-fold and DNA recovery rates of up to 2.4,% are achieved per round of selection. [source]

Mechanistic insights into oxidosqualene cyclizations through homology modeling

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 6 2003
Gasch, Tanja Schulz
Abstract 2,3-Oxidosqualene cyclases (OSC) are key enzymes in sterol biosynthesis. They catalyze the stereoselective cyclization and skeletal rearrangement of (3S)-2,3-oxidosqualene to lanosterol in mammals and fungi and to cycloartenol in algae and higher plants. Sequence information and proposed mechanism of 2,3-oxidosqualene cyclases are closely related to those of squalene-hopene cyclases (SHC), which represent functional analogs of OSCs in bacteria. SHCs catalyze the cationic cyclization cascade converting the linear triterpene squalene to fused ring compounds called hopanoids. High stereoselectivity and precision of the skeletal rearrangements has aroused the interest of researchers for nearly half a century, and valuable data on studying mechanistic details in the complex enzyme-catalyzed cyclization cascade has been collected. Today, interest in cyclases is still unbroken, because OSCs became targets for the development of antifungal and hypocholesterolemic drugs. However, due to the large size and membrane-bound nature of OSCs, three-dimensional structural information is still not available, thus preventing a complete understanding of the atomic details of the catalytic mechanism. In this work, we discuss results gained from homology modeling of human OSC based on structural information of SHC from Alicyclobacillus acidocaldarius and propose a structural model of human OSC. The model is in accordance with previously performed experimental studies with mechanism-based suicide inhibitors and mutagenesis experiments with altered activity and product specificity. Structural insight should strongly stimulate structure-based design of antifungal or cholesterol-lowering drugs. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 741,753, 2003 [source]

Multiple Pathways for the Irreversible Inhibition of Steroid Sulfatase with Quinone Methide-Generating Suicide Inhibitors

Measurement of inhibin A: a modification to an enzyme-linked immunosorbent assay

PRENATAL DIAGNOSIS, Issue 8 2001
Prema P. Thirunavukarasu
Abstract Inhibin A is a useful prenatal marker of Down syndrome. Currently, the available enzyme-linked immunosorbent assays (ELISAs) for inhibin A are based upon the same paired monoclonal antibodies. In the present study we have confirmed for one of those ELISAs that short-term sample storage as whole blood leads to a significant decline in detectable inhibin A and that this is most likely due to erythrocyte catalase interference with a critical oxidation step in the assay. While this interference can be eliminated by heating the samples pre-assay, this process is labour intensive. In the present study we have demonstrated that the addition of 3-amino-1,2,4-triazole (AT), a catalase ,suicide' inhibitor, also prevents the decline of inhibin A levels in samples stored as whole blood. We suggest that the addition of AT to samples prior to assay is a simple modification to the inhibin A ELISA that affords optimum performance. Copyright © 2001 John Wiley & Sons, Ltd. [source]