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


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.

SUBMITTER: Pastor MT 

PROVIDER: S-EPMC117354 | biostudies-literature | 2002 Jan

REPOSITORIES: biostudies-literature

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

Pastor Maria Teresa MT   López de la Paz Manuela M   Lacroix Emmanuel E   Serrano Luis L   Pérez-Payá Enrique E  

Proceedings of the National Academy of Sciences of the United States of America 20020108 2


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-a  ...[more]

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