N-(Hydroxyaminocarbonyl)phenylalanine:: A novel class of inhibitor for carboxypeptidase A

被引：18

作者：

Chung, SJ

Kim, DH

机构：

[1] Pohang Univ Sci & Technol, Ctr Biofunct Mol, Namgu, Pohang 790784, South Korea

[2] Pohang Univ Sci & Technol, Dept Chem, Namgu, Pohang 790784, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2001年 / 9卷 / 01期

关键词：

D O I：

10.1016/S0968-0896(00)00235-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

N-(Hydroxyaminocarbonyl)phenylalanine (1) was designed rationally as a new type of inhibitor for carboxypeptidase A (CPA). The designed inhibitor was readily prepared from phenylalnine benzyl ester in two steps and evaluated to find that rac-1 inhibits CPA in a competitive fashion with the K-i value of 2.09 muM. Surprisingly, inhibitor 1 having the D-configuration is more potent (K-i = 1.54 muM) than its antipode by about 3-fold. A possible explanation for the stereochemistry observed in the inhibition of CPA with 1 is presented. (C) 2000 Elsevier Science Ltd. All rights reserved.

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页码：185 / 189

页数：5

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共 23 条

[1] Modulators of leukotriene biosynthesis and receptor activation [J].

Brooks, CDW ;

Summers, JB .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (14) :2629-2654

[2] MATRILYSIN-INHIBITOR COMPLEXES - COMMON THEMES AMONG METALLOPROTEASES [J].

BROWNER, MF ;

SMITH, WW ;

CASTELHANO, AL .

BIOCHEMISTRY, 1995, 34 (20) :6602-6610

[3] BINDING OF BY-PRODUCT ANALOG BENZYLSUCCINIC ACID BY CARBOXYPEPTIDASE A [J].

BYERS, LD ;

WOLFENDEN, R .

BIOCHEMISTRY, 1973, 12 (11) :2070-2078

[4] CARBOXYPEPTIDASE-A [J].

CHRISTIANSON, DW ;

LIPSCOMB, WN .

ACCOUNTS OF CHEMICAL RESEARCH, 1989, 22 (02) :62-69

[5] X-RAY CRYSTALLOGRAPHIC INVESTIGATION OF SUBSTRATE BINDING TO CARBOXYPEPTIDASE-A AT SUBZERO TEMPERATURE [J].

CHRISTIANSON, DW ;

LIPSCOMB, WN .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (20) :7568-7572

[6] THE DETERMINATION OF ENZYME INHIBITOR CONSTANTS [J].

DIXON, M .

BIOCHEMICAL JOURNAL, 1953, 55 (01) :170-171

[7] THE 1ST MECHANISM-BASED INACTIVATORS FOR ANGIOTENSIN-CONVERTING ENZYME [J].

GHOSH, SS ;

SAIDNEJAD, O ;

ROESTAMADJI, J ;

MOBASHERY, S .

JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (22) :4175-4179

[8] INHIBITION OF MATRIX METALLOPROTEINASES BY HYDROXAMATES CONTAINING HETEROATOM-BASED MODIFICATIONS OF THE P-1' GROUP [J].

GOWRAVARAM, MR ;

TOMCZUK, BE ;

JOHNSON, JS ;

DELECKI, D ;

COOK, ER ;

GHOSE, AK ;

MATHIOWETZ, AM ;

SPURLINO, JC ;

RUBIN, B ;

SMITH, DL ;

PULVINO, T ;

WAHL, RC .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (14) :2570-2581

[9] BENZOTHIAZOLE HYDROXY UREAS AS INHIBITORS OF 5-LIPOXYGENASE - USE OF THE HYDROXYUREA MOIETY AS A REPLACEMENT FOR HYDROXAMIC ACID [J].

GRECO, MN ;

HAGEMAN, WE ;

POWELL, ET ;

TIGHE, JJ ;

PERSICO, FJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (17) :3180-3183

[10] METAL COMPLEXES OF 1-SUBSTITUTED 3-HYDROXYUREAS [J].

HARMON, RE ;

DABROWIA.JC ;

BROWN, DJ ;

GUPTA, SK ;

HERBERT, M ;

CHITHARA.D .

JOURNAL OF MEDICINAL CHEMISTRY, 1970, 13 (03) :577-&