Effects of chiral center on an all‐hydrocarbon tethered peptide

Abstract

Recently, our group reported that a precisely positioned chiral center on a thioether tether could dominate the backbone peptides' secondary structures and modulate the peptides' biophysical properties. Helical peptides constructed with this chirality induced helicity (CIH) method were named as CIH peptide. In this work, we examined the effects of substituting the thioether tether with an all hydrocarbon tether for the biophysical property differences. Two peptide epimers were prepared and showed distinct secondary structures and the R epimer is helical. Comparing with its thioether counterpart, the all‐hydrocarbon R epimer showed slightly higher helical content, modest improved binding affinity with mammal double minute 2 (MDM2), while similar cell permeability and slightly higher membrane toxicity.