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Titolo:
Development of plasma kallikrein selective inhibitors
Autore:
Okada, Y; Tsuda, Y; Tada, M; Wanaka, K; Hijikata-Okunomiya, A; Okamoto, U; Okamoto, S;
Indirizzi:
Kobe6512180,Univ, Fac Pharmaceut Sci, Dept Med Chem, Nishi Ku, Kobe, HyogoKobe Gakuin Univ Kobe Hyogo Japan 6512180 Med Chem, Nishi Ku, Kobe, Hyogo Kobe Res Projects Thrombosis & Haemostasis, Tarumi Ku, Kobe, Hyogo 6550033, Kobe Res Projects Thrombosis & Haemostasis Kobe Hyogo Japan 6550033 0033, 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
Titolo Testata:
BIOPOLYMERS
fascicolo: 1, volume: 51, anno: 1999,
pagine: 41 - 50
SICI:
0006-3525(1999)51:1<41:DOPKSI>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-LEUKOCYTE ELASTASE; THIOL PROTEINASE-INHIBITORS; ALPHA-CHYMOTRYPSIN; AMINO-ACIDS; CATHEPSIN-G; EGLIN-C; AFFINITY-CHROMATOGRAPHY; SYNTHETIC INHIBITOR; PURIFICATION METHOD; BLOOD-COAGULATION;
Keywords:
plasma kallikrein selective inhibitors; N-(trans-4-aminomethylcyclohexanecarbonyl)-phenylalanine-4-carboxymethylanilide (Tra-Phe-APAA); PKSI-Toyopearl; new affinity gel;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Okada, Y Kobe6512180,Univ, Fac Pharmaceut Sci, Dept Med Chem, Nishi Ku, Kobe, Hyogo Kobe Gakuin Univ Kobe Hyogo Japan 6512180 Nishi Ku, Kobe, Hyogo
Citazione:
Y. Okada et al., "Development of plasma kallikrein selective inhibitors", BIOPOLYMERS, 51(1), 1999, pp. 41-50

Abstract

During the course of the development of active center-directed plasmin inhibitors, it was found that N-(trans-4-aminomethylcyclohexanecarbonyl)-lysine-4-methoxycarbonylanilide inhibited plasma kallikrein more potently than other enzymes such as plasmin, urokinase, and thrombin although the inhibitory activity was not as potent and enzyme selectivity not as high. Based on studies of structure-activity relationship we designed and synthesized the plasma kallikrein selective inhibitor, N-(trans-4-aminomethylcyclohexanecarbonyl)-phenylalanine-4-carboxymethyl-anilide (Tra-Phe-APAA). Tra-Phe-APAA inhibited plasma kallikrein with a K-i value of 0.81 mu M, while it inhibited glandular kallikrein, plasmin, urokinase, tissue plasminogen activator factor Xa, factor XIIa, and thrombin with K-i values of > 500, 390 200 > 500 > 500 > 500, and > 500 mu M, respectively. We designated Tra-Phe-APAA as PKSI-527. Using PKSI-527 as an affinity ligand, we synthesized a new affinitygel (PKSI-Toyopearl) and employed it for the rapid purification of plasma kallikrein from human plasma. Human plasma activated with kaolin after acidtreatment was applied To a PKSI-527-Toyopearl column. Adsorbed protein waseluted with 50 mM glycine-hydrochloric acid buffer (pH 3.0). Plasma kallikrein was purified 181-fold with a yield of 85% from the kaolin-activated plasma. (C) 1999 John Wiley & Sons, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/10/20 alle ore 00:07:02