Mixture-Based Combinatorial Libraries from Small Individual Peptide Libraries: A Case Study on α1-Antitrypsin Deficiency

Molecules

Yi-Pin Chang¹ 

[1]The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA

关键词: antitrypsin;    alanine scanning;    conformational disease;    iterative deconvolution;    peptide library;    positional scanning;    split-and-mix;    surface plasmon resonance;    truncation library;    urea gel;   

DOI  :  10.3390/molecules19056330

来源: mdpi

【 摘 要 】

The design, synthesis and screening of diversity-oriented peptide libraries using a “libraries from libraries” strategy for the development of inhibitors of α₁-antitrypsin deficiency are described. The major buttress of the biochemical approach presented here is the use of well-established solid-phase split-and-mix method for the generation of mixture-based libraries. The combinatorial technique iterative deconvolution was employed for library screening. While molecular diversity is the general consideration of combinatorial libraries, exquisite design through systematic screening of small individual libraries is a prerequisite for effective library screening and can avoid potential problems in some cases. This review will also illustrate how large peptide libraries were designed, as well as how a conformation-sensitive assay was developed based on the mechanism of the conformational disease. Finally, the combinatorially selected peptide inhibitor capable of blocking abnormal protein aggregation will be characterized by biophysical, cellular and computational methods.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.