Paper Citing NAMD - Abstract
Speltz, Thomas E.; Fanning, Sean W.; Mayne, Christopher G.; Fowler, Colin; Tajkhorshid, Emad; Greene, Geoffrey L.; Moore, Terry W.
Stapled Peptides with -Methylated Hydrocarbon Chains for the Estrogen Receptor/Coactivator Interaction
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 55:4252-4255, MAR 18 2016
Stapled peptides are typically designed to replace two non-interacting residues with a constraining, olefinic staple. To mimic interacting leucine and isoleucine residues, we have created new amino acids that incorporate a methyl group in the -position of the stapling amino acid S5. We have incorporated them into a sequence derived from steroid receptor coactivator2, which interacts with estrogen receptor. The best peptide (IC50=89nm) replaces isoleucine689 with an S--methyl stapled amino acid, and has significantly higher affinity than unsubstituted peptides (390 and 760nm). Through X-ray crystallography and molecular dynamics studies, we show that the conformation taken up by the S--methyl peptide minimizes the syn-pentane interactions between the - and -methyl groups.
