Twists or Turns: stabilising alpha vs beta turns in tetrapeptides

Huy N. Hoang, Timothy Hill, Gloria Ruiz-Gómez, Frederik Diness, Jody Mason, Chongyang Wu, Giovanni Abbenante, nicholas Shepherd, David Fairlie

Research output: Contribution to journalArticle

Abstract

Protein-protein interactions involve hotspots as small as 4 sequential amino acids. Corresponding tetrapeptides have no structure in water. Here we report linking side chains of amino acids X and Z to form 24 cyclic tetrapeptides, cyclo-[XAAZ]-NH 2, and stabilise 14-18 membered rings that mimic different kinds of non-regular secondary structures found in protein hotspots. 2D NMR spectra allowed determination of 3D structures for 14 cyclic tetrapeptides in water. Five formed two (i, i + 3) hydrogen bonds and a beta/gamma (6, 7) or beta (9, 19, 20) turn; eight formed one (i, i + 4) hydrogen bond and twisted into a non-helical (13, 18, 21, 22, 24) or helical (5, 17, 23) alpha turn; one was less structured (15). A beta or gamma turn was favoured for Z = Dab, Orn or Glu due to a χ1 gauche (+) rotamer, while an alpha turn was favoured for Z = Dap (but not X = Dap) due to a gauche (-) rotamer. Surprisingly, an unstructured peptide ARLARLARL could be twisted into a helix when either a helical or non-helical alpha turn (5, 13, 17, 18, 21-24) with Z = Dap was attached to the N-terminus. These structural models provide insights into stability for different turns and twists corresponding to non-regular folds in protein hotspots.

Original languageEnglish
Article numberC9SC04153B
Pages (from-to)10595-10600
Number of pages6
JournalChemical Science
Volume10
Issue number45
Early online date3 Oct 2019
DOIs
Publication statusPublished - 7 Dec 2019

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Hoang, H. N., Hill, T., Ruiz-Gómez, G., Diness, F., Mason, J., Wu, C., ... Fairlie, D. (2019). Twists or Turns: stabilising alpha vs beta turns in tetrapeptides. Chemical Science, 10(45), 10595-10600. [C9SC04153B]. https://doi.org/10.1039/C9SC04153B

Twists or Turns: stabilising alpha vs beta turns in tetrapeptides. / Hoang, Huy N.; Hill, Timothy; Ruiz-Gómez, Gloria; Diness, Frederik; Mason, Jody; Wu, Chongyang; Abbenante, Giovanni; Shepherd, nicholas; Fairlie, David.

In: Chemical Science, Vol. 10, No. 45, C9SC04153B, 07.12.2019, p. 10595-10600.

Research output: Contribution to journalArticle

Hoang, HN, Hill, T, Ruiz-Gómez, G, Diness, F, Mason, J, Wu, C, Abbenante, G, Shepherd, N & Fairlie, D 2019, 'Twists or Turns: stabilising alpha vs beta turns in tetrapeptides', Chemical Science, vol. 10, no. 45, C9SC04153B, pp. 10595-10600. https://doi.org/10.1039/C9SC04153B
Hoang HN, Hill T, Ruiz-Gómez G, Diness F, Mason J, Wu C et al. Twists or Turns: stabilising alpha vs beta turns in tetrapeptides. Chemical Science. 2019 Dec 7;10(45):10595-10600. C9SC04153B. https://doi.org/10.1039/C9SC04153B
Hoang, Huy N. ; Hill, Timothy ; Ruiz-Gómez, Gloria ; Diness, Frederik ; Mason, Jody ; Wu, Chongyang ; Abbenante, Giovanni ; Shepherd, nicholas ; Fairlie, David. / Twists or Turns: stabilising alpha vs beta turns in tetrapeptides. In: Chemical Science. 2019 ; Vol. 10, No. 45. pp. 10595-10600.
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