Nonstereogenic α-aminoisobutyryl-glycyl dipeptidyl unit nucleates type I′ β-turn in linear peptides in aqueous solution

Larry R. Masterson, Marcus A. Etienne, Fernando Porcelli, George Barany, Robert P. Hammer, Gianluigi Veglia

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The use of α,α-disubstituted amino acids represents a valuable strategy to exercise conformational control in peptides. Incorporation of the nonstereogenic α-aminoisobutyryl-glycyl (Aib-Gly) dipeptidyl sequence into i + 1 and i + 2 positions of an acyclic peptide sequence, originally designed and investigated by Gellman and coworkers, [H-Arg-Tyr-Val-Glu-Val-Yyy-Xxx-Orn- Lys-Ile-Leu-Gln-NH2] nucleates a stable [2:4] left-handed type I′ β-turn in water. NMR spectra show that this newly designed β-hairpin does not aggregate in water up to a concentration of ∼ 1 mM, and that its backbone conformation is superimposable on corresponding hairpins containing the DPro-Gly (literature) and Aib-DAla (this work) sequences. The Aib-Gly turn-inducer sequence eliminates complications because of cis-trans isomerization of Zzz-Pro bonds, and constitutes an attractive alternative to the proteogenic Asn-Gly and nonproteogenic DPro-Gly motifs previously suggested as turn-inducer sequences. These design principles could be exploited to prepare water-soluble β-hairpin peptides with robust structures and novel function.

Original languageEnglish (US)
Pages (from-to)746-753
Number of pages8
JournalBiopolymers - Peptide Science Section
Volume88
Issue number5
DOIs
StatePublished - 2007

Keywords

  • C-disubstituted amino acids
  • Conformational analysis
  • NMR
  • Protein folding
  • α-aminoisobutyric acid
  • β-hairpin
  • β-turn

Fingerprint

Dive into the research topics of 'Nonstereogenic α-aminoisobutyryl-glycyl dipeptidyl unit nucleates type I′ β-turn in linear peptides in aqueous solution'. Together they form a unique fingerprint.

Cite this