期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：2
页码：614-619
DOI：10.1073/pnas.012583999
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 204 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.
