Facile and E-selective intramolecular ring-closing metathesis reactions in 310-helical peptides: A 3D structural study

Amie K. Boal, Ivan Guryanov, Alessandro Moretto, Marco Crisma, Erica L. Lanni, Claudio Toniolo, Robert H. Grubbs, Daniel J. O'Leary

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

The ring-closing metathesis reaction can be used to cross-link allylated serine residues situated at the i and i + 3 positions in 310-helical peptides containing the helicogenic amino acid, ∞-aminoisobutyric acid (Aib). An octapeptide with the sequence Boc-Aib-Aib-Aib-Ser(Al)-Aib-Aib-Ser(Al)-Aib-OMe was found to undergo a facile and >20:1 E-selective ring-closing metathesis (RCM) reaction catalyzed by the Grubbs second-generation catalyst to yield an 18-membered macrocycle. The formation of this cross-link does not significantly disturb the peptide's native 310-helicity, as judged by an X-ray diffraction study of the acyclic diene, the E-olefin RCM product, and its hydrogenated derivative. A heptapeptide system with the sequence Boc-Val-Ser(Al)-Leu-Aib-Ser(Al)-Val-Leu-OMe also underwent an efficient RCM reaction, albeit with diminished E-selectivity. It is apparent from these studies that a minimal, RCM-derived, macrocyclic constraint can be readily incorporated into 310-helical peptides.

Original languageEnglish (US)
Pages (from-to)6986-6987
Number of pages2
JournalJournal of the American Chemical Society
Volume129
Issue number22
DOIs
StatePublished - Jun 6 2007

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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