The role of disulfide bonds in structure and activity of chlorotoxin

被引：0

作者：

Ojeda, Paola G. ^{[1
]}

Chan, Lai Y. ^{[1
]}

Poth, Aaron G. ^{[1
]}

Wang, Conan K. ^{[1
]}

Craik, David J. ^{[1
]}

机构：

[1] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia

来源：

FUTURE MEDICINAL CHEMISTRY | 2014年 / 6卷 / 15期

基金：

英国医学研究理事会;

关键词：

CYSTINE KNOT; BACKBONE CYCLIZATION; LEIUROTOXIN-I; BRAIN-TUMORS; STABILITY; CYCLOTIDE; PEPTIDES; CONOTOXIN; SCORPION; GLIOMA;

D O I：

10.4155/FMC.14.93

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Background: Chlorotoxin is a small scorpion peptide that inhibits glioma cell migration. We investigated the importance of a major component of chlorotoxin's chemical structure-four disulfide bonds-to its tertiary structure and biological function. Results: Five disulfide bond analogs of chlorotoxin were synthesized, with l-a-aminobutyric acid residues replacing each or all of the disulfide bonds. Chemical oxidation and circular dichroism experiments revealed that Cys III-VII and Cys V-VIII were essential for native structure formation. Cys I-IV and Cys II-VI were important for stability of enzymatic proteolysis but not for the inhibition of human umbilical vein endothelial cell migration. Conclusion: The disulfide bonds of chlorotoxin are important for its structure and stability and have a minor role in its activity against cell migration.

引用

页码：1617 / 1628

页数：12

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