Cyclic pentapeptides as models for reverse turns: Determination of the equilibrium distribution between type I and type II conformations of Pro‐Asn and Pro‐Ala β‐turns

S. J. Stradley, Jose Rizo-Rey, M. D. Bruch, A. N. Stroup, L. M. Gierasch

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Cyclic pentapeptides are excellent models for reverse turns and have been used extensively in our laboratory to explore the influence of different amino acid sequences on turn preference. This paper is divided into two parts: In the first, we review our previous studies of cyclic pentapeptides. We summarize work that demonstrates the range of conformations possible within the cyclic pentapeptide backbone, the importance of sequence chirality in determining the backbone fold, and the utility of these cyclic pentapeptides as models for various turns. In the second, we present new results on two cyclic pentapeptides that contain β‐turns with Pro‐Ala or Pro‐Asn sequences in the i + 1 and i + 2 positions. By stereochemical criteria, a type I β‐turn is expected to be preferred by such L‐L sequences. On the other hand, in proteins Asn occurs frequently in the i + 2 position of type II turns. We asked whether the same propensity would be manifest in an isolated model peptide, and if so, what the interactions were that influenced the relative stability of the type I and type II turns. To address these questions we have compared the conformational behavior of two peptides: cyclo(Gly‐Pro‐Ala‐D‐Phe‐Pro) and cyclo(D‐Ala‐Pro‐Asn‐Gly‐Pro). From previous studies, we anticipated that both peptides would contain an inverse γ‐turn and a β‐turn which consisted of either Gly‐Pro‐Ala‐D‐Phe or D‐Ala‐Pro‐Asn‐Gly in positions i to i + 3, respectively. Nuclear magnetic resonance analysis confirms this overall backbone conformation. Furthermore, quantitative nuclear Overhauser effect measurements in combination with molecular dynamics simulations and torsionally‐forced energy minimizations have enabled us to determine that both type I and type II β‐turns are present in equilibrium in these peptides. The introduction of Asn in position i + 2 shifts this equilibrium significantly towards type II. We have done preliminary assessment of the possible side‐chain/backbone conformations that contribute to the shift in populations.

Original languageEnglish (US)
Pages (from-to)263-287
Number of pages25
JournalBiopolymers
Volume29
Issue number1
DOIs
StatePublished - Jan 1990

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

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