54582-05-7Relevant articles and documents
Penicillin G acylase-mediated kinetic resolution of racemic 1-(N-acylamino)alkylphosphonic and 1-(N-acylamino)alkylphosphinic acids and their esters
Zielińska, Katarzyna,Mazurkiewicz, Roman,Szymańska, Katarzyna,Jarz?bski, Andrzej,Magiera, Sylwia,Erfurt, Karol
, p. 31 - 40 (2016/07/19)
Extensive studies on the penicillin G acylase-mediated kinetic resolution of N-acylated 1-aminoalkylphosphonic and 1-aminoalkylphosphinic acids as well as their esters were carried out to recognise the relationships between the substrate structure, reacti
Optimization of amino acid thioesters as inhibitors of metallo-β-lactamase L1
Liu, Xiao-Long,Yang, Ke-Wu,Zhang, Yue-Juan,Ge, Ying,Xiang, Yang,Chang, Ya-Nan,Oelschlaeger, Peter
, p. 4698 - 4701 (2016/09/13)
The emergence of antibiotic resistance caused by metallo-β-lactamases (MβLs) is a global public health problem. Recently, we found amino acid thioesters to be a highly promising scaffold for inhibitors of the MβL L1. In order to optimize this series of inhibitors, nine new amino acid thioesters were developed by modifying the substituents on the N-terminus of the thioesters and the groups representing the amino acid side chain. Biological activity assays indicate that all of them are very potent inhibitors of L1 with an IC50value range of 20–600?nM, lower than those of most of the previously reported inhibitors of this scaffold. Analysis of structure–activity relationship reveals that big hydrophobic substituents on the N-terminus and a methionine amino acid side chain improves inhibitory activity of the thioesters. All these inhibitors are able to restore antibacterial activity of a β-lactam antibiotic against Escherichia coli BL21(DE3) cells producing L1 to that against E. coli cells lacking a β-lactamase. Docking studies reveal that a large N-terminal hydrophobic group results in a slightly different binding mode than smaller hydrophobic groups at the same position.
Resolution of α/β-amino acids by enantioselective penicillin G acylase from Achromobacter sp.
Grulich, Michal,Brezovsky, Jan,?těpánek, Václav,Palyzová, Andrea,Kyslíková, Eva,Kyslík, Pavel
, p. 240 - 247 (2015/10/28)
Penicillin G acylases (PGAs) are enantioselective enzymes catalyzing a hydrolysis of stable amide bond in a broad spectrum of substrates. Among them, derivatives of α- and β-amino acids represent a class of compounds with high application potential. PGAEc from Escherichia coli and PGAA from Achromobacter sp. CCM 4824 were used to catalyze enantioselective hydrolyses of seven selected N-phenylacetylated α/β-amino acid racemates. The PGAA showed higher stereoselectivity for enantiomers of N-PhAc-β-homoleucine, N-PhAc-α-tert-leucine and N-PhAc-β-leucine. To study the mechanism of enantiodiscrimination on molecular level, we have constructed a homology model of PGAA that was used in molecular docking experiments with the same substrates. In-silico experiments successfully reproduced the data from experimental enzymatic resolutions confirming validity of employed modeling protocol. We employed this protocol to evaluate enantiopreference of PGAA towards seven new substrates with application potential. For five of them, high enantioselectivity of PGAA was predicted.
The use of cellulose (chromatography paper) as a cheap, versatile and non-covalent support for organic molecules during multi-step synthesis
Shanahan, Stephen E.,Byrne, Douglas D.,Inglis, Graham G. A.,Alam, Mahbub,Macdonald, Simon J. F.
, p. 2554 - 2555 (2007/10/03)
Cellulose chromatography paper provides a novel non-covalent support for synthesis and in-situ purification of multi-dimensional arrays.
Rhodium-catalysed racemisation of N-acyl α-amino acids
Hateley, Martin J.,Schichl, Daniel A.,Kreuzfeld, Hans-J?rn,Beller, Matthias
, p. 3821 - 3824 (2007/10/03)
The first transition metal-catalysed racemisation of N-acyl α-amino acids, which is of importance for kinetic resolution processes, is described. Enantiomerically pure N-acyl α-amino acids were efficiently racemised under mild conditions using various rhodium complexes as catalysts, e.g. [Rh(cod)Cl]2, in the presence of phosphines. (C) 2000 Elsevier Science Ltd.
Structure-Activity Relationships in the Esterase-catalysed Hydrolysis and Transesterification of Esters and Lactones
Barton, Patrick,Laws, Andrew P.,Page, Michael I.
, p. 2021 - 2030 (2007/10/02)
The Broensted exponents for the alkaline hydrolysis of alkyl esters are 1.3 and 0.4 for substitution in the acyl and alcohol portions, respectively, which is indicative of a transition state which resembles the anionic tetrahedral intermediate with a localised negative charge.By contrast, the rate of the pig liver esterase (PLE)-catalysed hydrolysis shows little dependence upon the electron-withdrawing power of substituents.The values of kcat are independent of the pKa of the leaving group alcohol suggesting rate-limiting deacylation.There is a small steric effect of α-substitution in both the alcohol and carboxylic acid residues for the enzyme-catalysed reactions but the enzyme rate enhancement factor remains high for most esters.There is no substantial ee observed for the hydrolysis of racemic esters although the kinetic data can be used for determining the regioselective hydrolysis of diesters.Unsubstituted lactones are poor substrates for PLE but derivatives with hydrophobic substituents show kcat/Km values similar to those for acyclic esters.Dihydrocoumarin undergoes transesterification catalysed by PLE, kcat increases with increasing alcohol concentration indicative of rate-limiting deacylation.There is enantioselectivity in the PLE-catalysed hydrolysis of some racemic lactones but little or none in the transesterification of racemic alcohols with dihydrocoumarin.
