Identification of a potent analogue of nazumamide A through iteration of combinatorial tetrapeptide libraries

被引：13

作者：

Kundu, B ^{[1
]}

Bauser, M

Betschinger, J

Kraas, W

Jung, G

机构：

[1] Cent Drug Res Inst, Div Biopolymers, Lucknow 226001, Uttar Pradesh, India

[2] Univ Tubingen, Inst Organ Chem, D-72076 Tubingen, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 13期

关键词：

D O I：

10.1016/S0960-894X(98)00281-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Five sets of N-acylated tetrapeptide libraries and sublibraries related to Nazumamide A have been prepared using 25 natural and unnatural amino acids. They were evaluated in antithrombin assay, in order to quantify inhibition at each step of the tetrapeptide sublibrary iteration. The studies led to the identification of 2,5-dihydroxybenzoyl-lysyl-isoleucyl-phenylalanyl-arginine as a novel inhibitor of thrombin and was found to be at least 25 times more potent than the natural tetrapeptide 2,5- dihydroxybenzoyl-arginyl-prolyl-isoleucy-alpha-aminobutyric acid (NAZA). (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：1669 / 1672

页数：4

共 7 条

[1] Direct thrombin inhibitors in cardiovascular disease [J].

CatellaLawson, F .

CORONARY ARTERY DISEASE, 1997, 8 (02) :105-111

[2] THROMBIN ACTIVE-SITE INHIBITORS [J].

DAS, J ;

KIMBALL, SD .

BIOORGANIC & MEDICINAL CHEMISTRY, 1995, 3 (08) :999-1007

[3] BIOACTIVE MARINE METABOLITES .39. STEREOCHEMICAL CONTROL IN MICROBIAL REDUCTIONS .20. NAZUMAMIDE-A, A THROMBIN-INHIBITORY TETRAPEPTIDE, FROM A MARINE SPONGE, THEONELLA SP [J].

FUSETANI, N ;

NAKAO, Y ;

MATSUNAGA, S .

TETRAHEDRON LETTERS, 1991, 32 (48) :7073-7074

[4] SYNTHESIS OF NAZUMAMIDE-A, A THROMBIN-INHIBITORY LINEAR TETRAPEPTIDE, FROM A MARINE SPONGE, THEONELLA SP [J].

HAYASHI, K ;

HAMADA, Y ;

SHIOIRI, T .

TETRAHEDRON LETTERS, 1992, 33 (35) :5075-5076

[5]

JUNG G, 1996, COMBINATORIAL PEPTID

[6] A noncleavable retro-binding peptide that spans the substrate binding cleft of serine proteases. Atomic structure of nazumamide A: Human thrombin [J].

Nienaber, VL ;

Amparo, EC .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (29) :6807-6810

[7] Antithrombotics serine proteases [J].

Ripka, WC ;

Vlasuk, GP .

ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 32, 1997, 32 :71-89

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