title: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of València, València, E-46100 Burjassot, Spain.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Pastor
authors.forename: Manuela
authors.initials: M
authors.lastname: López de la Paz
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lacroix
authors.forename: Luis
authors.initials: L
authors.lastname: Serrano
authors.forename: Enrique
authors.initials: E
authors.lastname: Pérez-Payá
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D019151:Peptide Library; D010455:Peptides