Thomas Speltz
UIC
Hydrocarbon stapled peptides hold much promise as a general platform for inhibiting protein-protein interactions, but, beyond the substantial initial reports, relatively little research has gone into exploring the amino acids used for this technology. Guided by x-ray crystallography and molecular dynamics studies we have prepared a highly potent cell permeable stapled peptide that inhibits estrogen receptor activity in an MCF-7 breast cancer cell line, developed a novel bicyclic stapled peptide with improved proteolytic stability, and developed a stereoselective synthesis for preparing tether functionalized stapled peptides for targeting mutant estrogen receptor isoforms.