Stereochemical effects of all-hydrocarbon tethers in i,i+4 stapled peptides

Young Woo Kim, Gregory L. Verdine

Research output: Contribution to journalArticlepeer-review

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Abstract

The stereochemical effects of the hydrocarbon crosslink on the conformation and cellular uptake of i,i+4 stapled peptides were studied. Compared to its S,S-configurated counterpart, the crosslink bearing the R,R-configuration provided a significantly diminished helix stabilizing effect and conferred less efficient cellular uptake on the stapled peptides. These results suggest that the vesicular trafficking pathway employed by cells to take up stapled peptides is sensitive to the extent of helical character in the peptide, with greater helicity conferring increased cellular uptake.

Original languageEnglish
Pages (from-to)2533-2536
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number9
DOIs
StatePublished - 1 May 2009

Keywords

  • α-Helix
  • Cellular uptake mechanism
  • Helicity
  • Stapled peptides
  • Stereochemical effects

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