The synthesis of ketomethylene pseudopeptide analogues of dipeptide aldehyde inhibitors of calpain

被引：13

作者：

Angelastro, MR ^{[1
]}

Marquart, AL ^{[1
]}

Mehdi, S ^{[1
]}

Koehl, JR ^{[1
]}

Vaz, RJ ^{[1
]}

Bey, P ^{[1
]}

Peet, NP ^{[1
]}

机构：

[1] Hoechst Marion Roussel Inc, Bridgwater, NJ 08807 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1999年 / 9卷 / 02期

关键词：

D O I：

10.1016/S0960-894X(98)00704-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The ketomethylene phenylalanal and alanal analogues of Cbz-Val-Phe-H and Cbz-Val-Ala-H have been prepared and the K-i values versus chicken gizzard smooth muscle calpain were determined. The ketomethylene isosteres were significantly less potent than the corresponding dipeptide aldehydes, and this loss in activity is attributed to the absence of a critical interaction between the P1-P2 amide bond and the peptide binding region of calpain. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：139 / 140

页数：2

共 9 条

[1] ALPHA-DIKETONE AND ALPHA-KETO ESTER DERIVATIVES OF N-PROTECTED AMINO-ACIDS AND PEPTIDES AS NOVEL INHIBITORS OF CYSTEINE AND SERINE PROTEINASES [J].

ANGELASTRO, MR ;

MEHDI, S ;

BURKHART, JP ;

PEET, NP ;

BEY, P .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (01) :11-13

[2]

HONG SC, 1994, STROKE, V25, P669

[3] CRYSTAL-STRUCTURES OF RECOMBINANT RAT CATHEPSIN-B AND A CATHEPSIN B-INHIBITOR COMPLEX - IMPLICATIONS FOR STRUCTURE-BASED INHIBITOR DESIGN [J].

JIA, ZC ;

HASNAIN, S ;

HIRAMA, T ;

LEE, X ;

MORT, JS ;

TO, R ;

HUBER, CP .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (10) :5527-5533

[4] DIPEPTIDE ANALOGS - VERSATILE SYNTHESIS OF THE HYDROXYETHYLENE ISOSTERE [J].

KEMPF, DJ .

JOURNAL OF ORGANIC CHEMISTRY, 1986, 51 (21) :3921-3926

[5] Six-hour window of opportunity for calpain inhibition in focal cerebral ischemia in rats [J].

Markgraf, CG ;

Velayo, NL ;

Johnson, MP ;

McCarty, DR ;

Medhi, S ;

Koehl, JR ;

Chmielewski, PA ;

Linnik, MD .

STROKE, 1998, 29 (01) :152-158

[6] INHIBITION OF THE PROTEOLYSIS OF RAT ERYTHROCYTE-MEMBRANE PROTEINS BY A SYNTHETIC INHIBITOR OF CALPAIN [J].

MEHDI, S ;

ANGELASTRO, MR ;

WISEMAN, JS ;

BEY, P .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 157 (03) :1117-1123

[7] CELL-PENETRATING INHIBITORS OF CALPAIN [J].

MEHDI, S .

TRENDS IN BIOCHEMICAL SCIENCES, 1991, 16 (04) :150-153

[8] IDENTIFICATION OF A 3RD UBIQUITOUS CALPAIN SPECIES - CHICKEN MUSCLE EXPRESSES 4 DISTINCT CALPAINS [J].

SORIMACHI, H ;

TSUKAHARA, T ;

OKADABAN, M ;

SUGITA, H ;

ISHIURA, S ;

SUZUKI, K .

BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1995, 1261 (03) :381-393

[9] CALPAIN INHIBITION - AN OVERVIEW OF ITS THERAPEUTIC POTENTIAL [J].

WANG, KKW ;

YUEN, PW .

TRENDS IN PHARMACOLOGICAL SCIENCES, 1994, 15 (11) :412-419

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