beta-Peptides as inhibitors of protein-protein interactions.
We became interested several years ago in exploring whether 14-helical beta-peptide foldamers could bind protein surfaces and inhibit protein-protein interactions, and if so, whether their affinities and specificities would compare favorably with those of natural or miniature proteins. This exploration was complicated initially by the absence of a suitable beta-peptide scaffold, one that possessed a well-defined 14-helical structure in water and tolerated the diverse sequence variation required to generate high-affinity protein surface ligands. In this perspective, we describe our approach to the design of adaptable beta-peptide scaffolds with high levels of 14-helix structure in water, track the subsequent development of 14-helical beta-peptide protein-protein interaction inhibitors, and examine the potential of this strategy for targeting other therapeutically important proteins.
Kritzer
Joshua A
JA
Department of Chemistry, Yale University, New Haven, CT 06520, USA.
Stephens
Olen M
OM
Guarracino
Danielle A
DA
Reznik
Samuel K
SK
Schepartz
Alanna
A
D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry
D010455:Peptides; D011506:Proteins