Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemical syntheses of 2'(3')-O-(L-3-amino-3-phenylpropionyl)adenosine (2e), the corresponding D stereoisomer 2f, 2'(3')-O-(DL-phenylglycyl)adenosine (2g), 2'(3')-O-(N-benzylglycyl)adenosine (2h), and 9(2-O-L-phenylalanyl-beta-D-xylofuranosyl)adenine (3b) are described. Compounds 2e-h were obtained by acylation of 5'-O-(4-methoxytrityl)adenosine with the appropriate N-benzyloxycarbonyl or N-tert-butoxycarbonyl amino acids with dicyclohexylcarbodiimide in pyridine. The corresponding reaction of N-(benzyloxycarbonyl)-D-phenylglycine led to an almost complete racemization of the aminoacyl residue (compounds 2c and 2g). Subsequent chromatographic separation and deprotection of intermediates 2a-d afforded the desired target derivatives 2e-h. Product 3b was obtained by a similar acylation of 9-(3,5-O-isopropylidene-beta-D-xylofuranosyl)adenine with N-(benzyloxycarbonyl)-L-phenylalanine, followed by deblocking. The NMR spectra of 2' and 3' isomers of stereoisomers 2a and 2b are discussed. Compounds 2g and 3b are both substrates and inhibitors of Escherichia coli ribosomal peptidyltransferase, although the activity of 3b is low. Derivatives 2e,f,h do not accept AcPhe from N-AcPhe-tRNA in a peptidyltransferase-catalyzed reaction, but they inhibit the puromycin reaction in the same system. The order of inhibitory activity is 2e greater than 2f greater than 2h. The implications of these findings for the mechanism of peptidyltransferase and comparison of the latter with the action of chymotrypsin are discussed.
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PMID:Analogues of 2'(3')-O-L-phenylalanyladenosine as substrates and inhibitors of ribosomal peptidyltransferase. 633 35

Phenylpropynal is a specific, irreversible, non-beta-lactam inhibitor of typical beta-lactamases. In the presence of millimolar concentrations of phenylpropynal, the beta-lactamase I of Bacillus cereus and the beta-lactamases of Staphylococcus aureus and Escherichia coli become completely inactivated; the beta-lactamase II of B. cereus is not affected. The E. coli beta-lactamase is considerably more sensitive to the reagent than the gram-positive enzymes. A variety of structural analogs of phenylpropynal are much less effective inhibitors. Bovine alpha-chymotrypsin, bovine carboxypeptidase A, and the D,D-carboxypeptidase/transpeptidase of Streptomyces R-61 were not inactivated by phenylpropynal. The inactivation of the E. coli beta-lactamase can be significantly retarded when the good substrate benzylpenicillin is also present. The development of a characteristic chromophore (lambda max 318 nm) during beta-lactamase inactivation suggests that covalent modification of the enxymes is involved; arginine and/or lysine modification is indicated.
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PMID:Phenylpropynal, a specific, irreversible, non-beta-lactam inhibitor of beta-lactamases. 676 45

Two large polypeptide fragments of ribosomal protein L16 were obtained by limited hydrolysis with trypsin and chymotrypsin. The chymotryptic fragment, lacking nine N-terminal amino acids residues, is fully active in the restoration of the peptidyltransferase activity of the LiCl-stripped 50-S ribosomal subunits, whereas the tryptic fragment, lacking an additional six residues, is inactive. We also show that under the optimized ionic conditions protein L16 is not needed for the peptidyltransferase activity.
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PMID:The role of protein L16 and its fragments in the peptidyltransferase activity of 50-S ribosomal subunits. 688 53

The structural and functional organization of Escherichia coli polypeptide chain release factors 1 and 2 (RF-1 and RF-2) was investigated by limited proteolysis with trypsin and chymotrypsin. A protease-sensitive site was found in a similar position in both factors at the beginning of a highly conserved region in the C-terminal part of the proteins. Chymotrypsin cleavage of RF-2 yielded a nicked form with the fragments associated. This nicked factor lost in vitro peptidyl-tRNA hydrolysis activity (a peptidyltransferase function) but had enhanced in vitro codon-ribosome binding activity (a decoding site function). It inhibited codon-dependent f[3H]Met-tRNA hydrolysis activity of intact RF-1 and RF-2, presumably as a result of an increased affinity for ribosomes. These data are consistent with a model whereby the release factor acts like a tRNA analog spanning the decoding and peptidyltransferase centers on the ribosome. The proteolytic sensitivity of the RFs most likely reflects an exposed surface loop. We propose that this loop interacts with the ribosomal peptidyltransferase site and that the stabilization of factor:ribosome binding upon cleavage could be explained by conformational coupling between domains on the factor for codon-ribosome binding at the decoding site and interaction with peptidyltransferase.
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PMID:A single proteolytic cleavage in release factor 2 stabilizes ribosome binding and abolishes peptidyl-tRNA hydrolysis activity. 803 46

The aim of this study was to encapsulate glutathione (GSH) alone or in combination with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in Eudragit RS 100 microparticles (MPs), and to evaluate these novel delivery systems for oral administration of the considered tripeptide. The MPs were prepared by an O/O emulsion-solvent evaporation method according to a multilevel experimental design involving the volume of liquid paraffin, the HP-beta-CD amount, and the drug/polymer ratio as independent variables. The effects of these parameters on particle size, entrapment efficiency, and drug release were investigated. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) analysis and differential scanning calorimetry (DSC) studies were performed to evaluate possible interactions between GSH and Eudragit RS 100 polymer and to characterize the physical state of drug within the MPs. The release profiles of GSH from MPs were examined in vitro at pH 1.2, 6.8. and 7.4 using the USP III (BioDis) dissolution apparatus. In general, a slow and zero-order release of GSH from MPs at pH 1.2 occurred, while at higher pH values considerable amounts of glutathione disulfide (i.e., GSSG) were observed. The enzymatic stability and the intestinal permeability of some GSH-containing MPs were assessed by using pepsin, alpha-chymotrypsin, gamma-glutamyl-transpeptidase and everted frog intestinal sac methodology, respectively. The results suggest that GSH-loaded Eudragit RS 100 MPs containing HP-beta-CD represent a new sustained GSH delivery system useful for the oral administration of the examined tripeptide.
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PMID:Eudragit RS 100 microparticles containing 2-hydroxypropyl-beta-cyclodextrin and glutathione: physicochemical characterization, drug release and transport studies. 1711 31