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.
Combinatorial approaches: a new tool to search for highly structured beta-hairpin peptides.,Pastor MT, Lopez de la Paz M, Lacroix E, Serrano L, Perez-Paya E Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):614-9. Epub 2002 Jan 8. PMID:11782528[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
↑ Pastor MT, Lopez de la Paz M, Lacroix E, Serrano L, Perez-Paya E. Combinatorial approaches: a new tool to search for highly structured beta-hairpin peptides. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):614-9. Epub 2002 Jan 8. PMID:11782528 doi:10.1073/pnas.012583999
