Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Z-D-Phe-Pro-boroMpg-OPin (9a)1,2 has been shown previously to be a highly specific inhibitor of thrombin in spite of lacking an arginine-like guanidino group at the P1 site. A range of compounds have been synthesized based upon this lead compound, varying the neutral side chain at the P1 site. Of the 20 examples based upon the structures at P2 and P3 of Z-D-X-Pro (X being Phe or beta,beta-diphenylalanine), all were found to be effective inhibitors of thrombin (Ki's between 10 and 100 nM). Furthermore all exhibited a high specificity toward thrombin having values for a Ki(trypsin)/Ki(thrombin) ratio of between 10- and 100-fold. High ratio values were found for a number of the compounds tested against a range of serine proteinases (plasmin, factor Xa, kallikrein, urokinase, protein Ca, chymotrypsin, elastase, and cathepsin G). As far as potency toward thrombin, compounds containing the methoxypropyl group at P1 were favored over those with a methoxy grouping on a shorter alkyl chain (8) or without the methoxy group (1-5). The compounds display potent anticoagulant activity with values for 18 in thrombin time of 0.63 microM and in activated partial thromboplastin time of 2.0 microM. 11B NMR has been used to confirm interaction of the boron atom with the active site. From the high specificity shown with all the compounds we propose that the compounds, constitute a new class of thrombin inhibitors.
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PMID:Characterization of a class of peptide boronates with neutral P1 side chains as highly selective inhibitors of thrombin. 773 10

In this study we characterized a bacteriocin, warnericin RB4, produced by Staphylococcus warneri RB4. Warnericin RB4 activity was completely inactivated by trypsin and actinase E. The activity was stable at 100 degrees C for 15 min, and had a pH range of 2 to 6. S. warneri RB4 showed antibacterial activity against only Alicyclobacillus acidoterrestris, A. acidocaldarius, and Micrococcus luteus, among 34 bacterial species tested. The amino acid sequence of the purified bacteriocin contained 27 amino acid residues (K-K-K-S-G-V-I-P-X-V-X-H-D-X-H-M-N-X-F-Q-F-V-F-X-X-X-S). The molecular mass of the bacteriocin was estimated to be 2,958.2 Da by ESI-MS. These results show that the Warnericin RB4 exhibiting specific antibacterial activity against thermo-acidophiles, Alicyclobacillus spp., is a Nukacin ISK-1 or closely related bacteriocin, classified with class IA (Lacticin 481 types). This is the first report that Warnericin RB-4 is effective to inhibit the growth of causative microorganisms of spoilage in various acidic drinks. Warnericin RB4 might prove useful in fruit juices and fruit juice-containing drinks.
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PMID:Purification and characterization of Warnericin RB4, anti-Alicyclobacillus bacteriocin, produced by Staphylococcus warneri RB4. 1597 Oct 94