ATP-conjugated peptide inhibitors for calmodulin-dependent protein kinase II

被引：11

作者：

Ahn, Dae-Ro ^{[1
]}

Han, Ki-Cheol ^{[1
]}

Kwon, Hyuk Sung ^{[1
]}

Yang, Eun Gyeong ^{[1
]}

机构：

[1] Korea Inst Sci & Technol, Div Life Sci, Seoul 136650, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 01期

关键词：

bisubstrate analog inhibitors; ATP-conjugated peptide inhibitors; calmodulin-dependent protein kinase II;

D O I：

10.1016/j.bmcl.2006.09.070

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Substrate analog peptides of CaMKII with varying degrees of the inhibitory potency were linked to ATP gamma S either by considering a phosphoryl transfer mechanism or simply by using a relatively long flexible linker. The latter bisubstrate inhibitors showed relatively little effects while the former ones improved inhibitory potency to different levels depending on the binding affinities of the peptide moieties. One of the mechanism-based bisubstrate inhibitors was then utilized to demonstrate an ATP-competitive but peptide substrate-uncompetitive inhibition, supporting an ordered binding mechanism for CaMKII (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：147 / 151

页数：5

共 18 条

[1] RATIONAL DESIGN OF ENZYME-INHIBITORS - MULTISUBSTRATE ANALOG INHIBITORS [J].

BROOM, AD .

JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (01) :2-7

[2]

HANSON PI, 1992, J BIOL CHEM, V267, P17216

[3] Design, synthesis, and characterization of an ATP-peptide conjugate inhibitor of protein kinase A [J].

Hines, AC ;

Cole, PA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (11) :2951-2954

[4] Structure-function of the multifunctional Ca2+/calmodulin-dependent protein kinase II [J].

Hudmon, A ;

Schulman, H .

BIOCHEMICAL JOURNAL, 2002, 364 (03) :593-611

[5] Neuronal Ca2+/calmodulin-dependent protein kinase II:: The role of structure and autoregulation in cellular function [J].

Hudmon, A ;

Schulman, H .

ANNUAL REVIEW OF BIOCHEMISTRY, 2002, 71 :473-510

[6] Critical amino acid residues of AIP, a highly specific inhibitory peptide of calmodulin-dependent protein kinase II [J].

Ishida, A ;

Shigeri, Y ;

Tatsu, Y ;

Uegaki, K ;

Kameshita, I ;

Okuno, S ;

Kitani, T ;

Yumoto, N ;

Fujisawa, H .

FEBS LETTERS, 1998, 427 (01) :115-118

[7] STABILIZATION OF CALMODULIN-DEPENDENT PROTEIN-KINASE-II THROUGH THE AUTOINHIBITORY DOMAIN [J].

ISHIDA, A ;

FUJISAWA, H .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (05) :2163-2170

[8] NOVEL HIGHLY SPECIFIC AND POTENT INHIBITOR OF CALMODULIN-DEPENDENT PROTEIN-KINASE-II [J].

ISHIDA, A ;

KAMESHITA, I ;

OKUNO, S ;

KITANI, T ;

FUJISAWA, H .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 212 (03) :806-812

[9] KINETIC MECHANISM OF THE TYPE-II CALMODULIN-DEPENDENT PROTEIN-KINASE - STUDIES OF THE FORWARD AND REVERSE REACTIONS AND OBSERVATION OF APPARENT RAPID-EQUILIBRIUM ORDERED BINDING - APPENDIX - VARIOUS CASES OF RAPID-EQUILIBRIUM ORDERED BIREACTANT MECHANISMS - THEIR BASES AND DIFFERENTIATION [J].

KWIATKOWSKI, AP ;

HUANG, CY ;

KING, MM ;

HUANG, CY .

BIOCHEMISTRY, 1990, 29 (01) :153-159

[10] A bisubstrate analog inhibitor of the carboxyltransferase component of acetyl-CoA carboxylase [J].

Levert, KL ;

Waldrop, GL .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 291 (05) :1213-1217

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