Stabilization of Cyclic β-Hairpins by Ugi-Reaction-Derived N-Alkylated Peptides: The Quest for Functionalized β-Turns

Org Lett. 2019 Sep 20;21(18):7307-7310. doi: 10.1021/acs.orglett.9b02592. Epub 2019 Sep 4.

Abstract

A solid-phase approach including on-resin Ugi reactions was developed for the construction of β-hairpins. Various N-alkylated dipeptide fragments proved capable of aligning antiparallel β-sheets in a macrocyclic scaffold, thus serving as β-hairpin templates. Gramicidin S was used as the model β-hairpin to compare the Ugi-derived β-turns with the type-II' β-turn. The results show that the multicomponent incorporation of such N-alkylated residues allows for the simultaneous stabilization and exo-cyclic functionalization of cyclic β-hairpins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Dipeptides / chemical synthesis
  • Dipeptides / chemistry*
  • Gramicidin / chemical synthesis*
  • Gramicidin / chemistry
  • Molecular Conformation
  • Protein Stability
  • Protein Structure, Secondary
  • Solid-Phase Synthesis Techniques

Substances

  • Dipeptides
  • Gramicidin