KINETIC CHARACTERIZATION OF A PEPTIDE INHIBITOR OF TRYPSIN ISOLATED FROM A SYNTHETIC PEPTIDE COMBINATORIAL LIBRARY

被引:5
作者
COOMBS, GS [1 ]
HAZZARD, J [1 ]
COREY, DR [1 ]
机构
[1] UNIV TEXAS,SW MED CTR,HOWARD HUGHES MED INST,DEPT PHARMACOL,DALLAS,TX 75235
关键词
D O I
10.1016/0960-894X(95)00082-5
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Recently Eichler and Houghten(1) have described the use of a combinatorial peptide library to optimize small trypsin inhibitors. Our kinetic analysis of the most inhibitory peptide, YYGAKIYRPDKM, reveals that it is an inefficiently cleaved substrate for trypsin due to a low k(cat), possesses a relatively low K-M, and may exhibit nonproductive binding.
引用
收藏
页码:611 / 614
页数:4
相关论文
共 8 条
[1]   A SOLUTION-PHASE SCREENING-PROCEDURE FOR THE ISOLATION OF ACTIVE COMPOUNDS FROM A LIBRARY OF MOLECULES [J].
CARELL, T ;
WINTNER, EA ;
REBEK, J .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1994, 33 (20) :2061-2064
[2]   AN INVESTIGATION INTO THE MINIMUM REQUIREMENTS FOR PEPTIDE HYDROLYSIS BY MUTATION OF THE CATALYTIC TRIAD OF TRYPSIN [J].
COREY, DR ;
CRAIK, CS .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1992, 114 (05) :1784-1790
[3]   IDENTIFICATION OF SUBSTRATE-ANALOG TRYPSIN-INHIBITORS THROUGH THE SCREENING OF SYNTHETIC PEPTIDE COMBINATORIAL LIBRARIES [J].
EICHLER, J ;
HOUGHTEN, RA .
BIOCHEMISTRY, 1993, 32 (41) :11035-11041
[4]   SUBSTRATE-SPECIFICITY OF TRYPSIN INVESTIGATED BY USING A GENETIC SELECTION [J].
EVNIN, LB ;
VASQUEZ, JR ;
CRAIK, CS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (17) :6659-6663
[5]  
FINKENSTADT WR, 1974, BAYER S, V5, P389
[6]   PROTEIN INHIBITORS OF PROTEINASES [J].
LASKOWSKI, M ;
KATO, I .
ANNUAL REVIEW OF BIOCHEMISTRY, 1980, 49 :593-626
[7]   DESIGN AND CHARACTERIZATION OF AN INTRAMOLECULAR ANTIPARALLEL COILED-COIL PEPTIDE [J].
MYSZKA, DG ;
CHAIKEN, IM .
BIOCHEMISTRY, 1994, 33 (09) :2363-2372
[8]   ROLE OF THE S' SUBSITES IN SERINE-PROTEASE CATALYSIS - ACTIVE-SITE MAPPING OF RAT CHYMOTRYPSIN, RAT TRYPSIN, ALPHA-LYTIC PROTEASE, AND CERCARIAL PROTEASE FROM SCHISTOSOMA-MANSONI [J].
SCHELLENBERGER, V ;
TURCK, CW ;
RUTTER, WJ .
BIOCHEMISTRY, 1994, 33 (14) :4251-4257