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RESEARCH PRODUCT
Combinatorial approaches: A new tool to search for highly structured β-hairpin peptides
Manuela López De La PazEmmanuel LacroixEnrique Pérez-payáLuis SerranoMaría Teresa Pastorsubject
Models MolecularProtein FoldingCircular dichroismMagnetic Resonance SpectroscopyFold (higher-order function)Molecular Sequence DataPopulationPeptideComputational biologyBiologyProtein Structure SecondaryPeptide LibraryCombinatorial Chemistry TechniquesAmino Acid Sequenceeducationchemistry.chemical_classificationeducation.field_of_studyMultidisciplinaryCircular DichroismBiological SciencesCombinatorial chemistryTemplatechemistryDrug DesignDeconvolutionPeptidesdescription
Here we present a combinatorial approach to evolve a stable β-hairpin fold in a linear peptide. Starting with a de novo -designed linear peptide that shows a β-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 β-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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2002-01-08 | Proceedings of the National Academy of Sciences |