Stereochemical effects of all-hydrocarbon tethers in i,i+4 stapled peptides.
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.
Kim
Young-Woo
YW
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
Verdine
Gregory L
GL