Designing helical peptide inhibitors of protein-protein interactions.
Short helical peptides combine characteristics of small molecules and large proteins and provide an exciting area of opportunity in protein design. A growing number of studies report novel helical peptide inhibitors of protein-protein interactions. New techniques have been developed for peptide design and for chemically stabilizing peptides in a helical conformation, which frequently improves protease resistance and cell permeability. We summarize advances in peptide crosslinking chemistry and give examples of peptide design studies targeting coiled-coil transcription factors, Bcl-2 family proteins, MDM2/MDMX, and HIV gp41, among other targets.
MIT Department of Biology, 77 Massachusetts Avenue, Cambridge, MA 02139, United States.
Raheleh
R
Rezaei Araghi
MIT Department of Biology, 77 Massachusetts Avenue, Cambridge, MA 02139, United States; MIT Department of Biological Engineering, 77 Massachusetts Avenue, Cambridge, MA 02139, United States. Electronic address: keating@mit.edu.
Amy E
AE
Keating
D000818:Animals; D015195:Drug Design; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D000072756:Protein Conformation, alpha-Helical; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
D010455:Peptides; D011506:Proteins