Combinatorial approaches: a new tool to search for highly structured beta-hairpin peptides

Proceedings of the National Academy of Sciences of the United States of America
M Teresa PastorEnrique Pérez-Payá

Abstract

Here we present a combinatorial approach to evolve a stable beta-hairpin fold in a linear peptide. Starting with a de novo-designed linear peptide that shows a beta-hairpin structure population of around 30%, we selected four positions to build up a combinatorial library of 20(4) sequences. Deconvolution of the library using circular dichroism reduced such a sequence complexity to 36 defined sequences. Circular dichroism and NMR of these peptides resulted in the identification of two linear 14-aa-long peptides that in plain buffered solutions showed a percentage of beta-hairpin structure higher than 70%. Our results show how combinatorial approaches can be used to obtain highly structured peptide sequences that could be used as templates in which functionality can be introduced.

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Citations

May 3, 2003·Current Opinion in Structural Biology·S GnanakaranAngel E García
May 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Brandon L KierNiels H Andersen
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Apr 14, 2020·Journal of Chemical Theory and Computation·Fang-Yu LinAlexander D MacKerell

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