Stabilizing capping motif for beta-hairpins and sheets.
Although much has been learned about the design of models of beta-sheets during the last decade, modest fold stabilities in water and terminal fraying remain a feature of most beta-hairpin peptides. In the case of hairpin capping, nature did not provide guidance for solving the problem. Some observations from prior turn capping designs, with further optimization, have provided a generally applicable, "unnatural" beta cap motif (alkanoyl-Trp at the N terminus and Trp-Thr-Gly at the C terminus) that provides a net contribution of 6 + kJ/mol to beta-hairpin stability, surpassing all other interactions that stabilize beta-hairpins including the covalent disulfide bond. The motif, made up entirely of natural residues, is specific to the termini of antiparallel beta-strands and reduces fraying at the ends of hairpins and other beta-sheet models. Utilizing this motif, 10- to 22-residue peptide scaffolds of defined stereochemistry that are greater than 98% folded in water have been prepared. The beta-cap can also be used to staple together short antiparallel beta-strands connected by a long flexible loop.
Kier
Brandon L
BL
Department of Chemistry, University of Washington, Seattle WA 98195, USA.
Shu
Irene
I
Eidenschink
Lisa A
LA
Andersen
Niels H
NH
D000107:Acetylation; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
D011506:Proteins