Total chemical synthesis of bovine pancreatic trypsin inhibitor by native chemical ligation

FEBS Letters

Lu, Wuyuan¹  Kent, Stephen B.H¹  Starovasnik, Melissa A² 

[1] Gryphon Sciences, 250 East Grand Avenue, Suite 90, South San Francisco, CA 94080, USA;Department of Protein Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA

关键词: Bovine pancreatic trypsin inhibitor;    Solid phase peptide synthesis;    Native chemical ligation;   

DOI  :  10.1016/S0014-5793(98)00547-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Bovine pancreatic trypsin inhibitor (BPTI) is an important model for the study of protein folding. Herein we describe a robust approach to the total chemical synthesis of BPTI using native chemical ligation of unprotected peptide segments in aqueous solution. After refolding and oxidative formation of disulfides, the target protein was purified by affinity chromatography. The synthetic BPTI was characterized by mass spectrometry, inhibition assay, thermal denaturation and 2D NMR spectroscopy, and was shown to be structurally and functionally identical to natural BPTI. The synthetic strategy presented in this paper has enabled us to establish rapid access to novel analogues of BPTI.

【 授权许可】

Unknown