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Titolo:
Selective inhibition of Trypsin by (2R,4R)-4-Phenyl-1-[N-alpha-(7-methoxy-2-naphthalenesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid
Autore:
Hijikata-Okunomiya, A; Tamao, Y; Kikumoto, R; Okamoto, S;
Indirizzi:
Kobe Univ, Sch Med, Fac Hlth Sci, Suma Ku, Kobe, Hyogo 6540142, Japan KobeUniv Kobe Hyogo Japan 6540142 i, Suma Ku, Kobe, Hyogo 6540142, Japan Mitsubishi Tokyo Pharmaceut Inc, Yokohama Res Ctr, Aoba Ku, Yokohama, Kanagawa 2270033, Japan Mitsubishi Tokyo Pharmaceut Inc Yokohama Kanagawa Japan 2270033 33, Japan Kobe Res Projects Thrombosis & Hemostasis, Tarumi Ku, Kobe, Hyogo 6550033,Japan Kobe Res Projects Thrombosis & Hemostasis Kobe Hyogo Japan 6550033 ,Japan
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 25, volume: 275, anno: 2000,
pagine: 18995 - 18999
SICI:
0021-9258(20000623)275:25<18995:SIOTB(>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN ALPHA-THROMBIN; HUMAN-LUNG TRYPTASE; CRYSTAL-STRUCTURE; ACTIVE-SITES; ARGININE; BENZAMIDINE; DERIVATIVES; RESOLUTION; COMPLEXES; GEOMETRY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Hijikata-Okunomiya, A Kobe Univ, Sch Med, Fac Hlth Sci, Suma Ku, Tomogaoka7-10-2, Kobe, Hyogo 6540142, Japan Kobe Univ Tomogaoka 7-10-2 Kobe Hyogo Japan 6540142
Citazione:
A. Hijikata-Okunomiya et al., "Selective inhibition of Trypsin by (2R,4R)-4-Phenyl-1-[N-alpha-(7-methoxy-2-naphthalenesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid", J BIOL CHEM, 275(25), 2000, pp. 18995-18999

Abstract

Evidence is accumulating indicating that trypsin stimulates divergent cellular reactions through the proteinase-activated receptor, in addition to its role as the digestive enzyme. In this report, we introduce (2R,4R)-4-phenyl-1-[N-alpha-(7-methoxy-2-naphthalenesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid as a potent and selective trypsin inhibitor. The agent inhibited trypsin competitively with the K-i value of 0.1 mu M. It inhibited thrombin weakly (K-i = 2 mu M) and did not inhibit plasmin, plasma kallikrein, urokinase, and mast cell tryptase (K-i values for these enzymes are >60 mu M). Comparative studies with several established proteinase inhibitors revealed that the compound was the first small molecular weight trypsin inhibitorwithout tryptase inhibitory activity. A docking study has provided a plausible explanation for the molecular mechanism of the selective inhibition showing that the agent fits into the active site of trypsin without any severe collision but that it comes into clash at the 4-phenyl group of piperidine ring against the "60-insertion loop" of thrombin and at the 7-methoxy-2-naphthalenesulfonyl group against Gln(98) of tryptase.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/10/20 alle ore 01:31:11