A new turn structure for the formation of beta-hairpins in peptides.
Previous studies by Gellman and co-workers have elegantly shown that mirror-image beta-turns based upon d-Pro-Gly are especially good at stabilizing beta-hairpins and have demonstrated that peptide 1 [Arg-Trp-Gln-Tyr-Val-d-Pro-Gly-Lys-Phe-Thr-Val-Gln-NH2] folds into a well-defined beta-hairpin [Espinosa, J. F.; Gellman, S. H. Angew. Chem., Int. Ed. 2000, 39, 2330-2333]. The present study establishes that the amino acid ornithine (Orn) also forms a turn structure that is excellent at stabilizing beta-hairpins when linked through the delta-amino group and that this turn is comparable to d-Pro-Gly in ability to induce beta-hairpin formation. Thus, 1H NMR chemical shift and NOE studies establish that Orn-containing analogue 2 [Arg-Trp-Gln-Tyr-Val-deltaOrn-Lys-Phe-Thr-Val-Gln-NH2] is comparable in structure to peptide 1. The present study also establishes that the Orn turn is superior to Asn-Gly turns and that replacement of the deltaOrn with epsilonLys or d-deltaOrn generates structures that do not fold significantly.
Nowick
James S
JS
Department of Chemistry, University of California-Irvine, Irvine, CA 92697-2025, USA. jsnowick@uci.edu
Brower
Justin O
JO
D021542:Amino Acids, Neutral / Q000737:chemistry; D005998:Glycine / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D009952:Ornithine / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding
D021542:Amino Acids, Neutral; D009842:Oligopeptides; C013809:5-aminovaleric acid; D011392:Proline; D009952:Ornithine; D005998:Glycine