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Molecules 2014, 19(5), 6330-6348; doi:10.3390/molecules19056330
Review

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

1 and 2,*
Received: 7 February 2014; in revised form: 12 May 2014 / Accepted: 13 May 2014 / Published: 16 May 2014
(This article belongs to the Special Issue Combinatorial Synthesis)
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Abstract: 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.
Keywords: antitrypsin; alanine scanning; conformational disease; iterative deconvolution; peptide library; positional scanning; split-and-mix; surface plasmon resonance; truncation library; urea gel antitrypsin; alanine scanning; conformational disease; iterative deconvolution; peptide library; positional scanning; split-and-mix; surface plasmon resonance; truncation library; urea gel
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Chang, Y.-P.; Chu, Y.-H. Mixture-Based Combinatorial Libraries from Small Individual Peptide Libraries: A Case Study on α1-Antitrypsin Deficiency. Molecules 2014, 19, 6330-6348.

AMA Style

Chang Y-P, Chu Y-H. Mixture-Based Combinatorial Libraries from Small Individual Peptide Libraries: A Case Study on α1-Antitrypsin Deficiency. Molecules. 2014; 19(5):6330-6348.

Chicago/Turabian Style

Chang, Yi-Pin; Chu, Yen-Ho. 2014. "Mixture-Based Combinatorial Libraries from Small Individual Peptide Libraries: A Case Study on α1-Antitrypsin Deficiency." Molecules 19, no. 5: 6330-6348.



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