Solid-phase syntheses of beta-turn analogues to mimic or disrupt protein-protein interactions.
Protein-protein interactions are difficult targets in medicinal chemistry, but they will become increasingly important as data from The Human Genome Project is interpreted. Our work focuses on beta-turn mimics that are designed to mimic or disrupt some of these interactions. Solid-phase syntheses and preferred conformations of beta-turn mimics that incorporate dipeptide units are discussed. The activity of one illustrative compound that potentiates the interaction of the nerve growth factor with its transmembrane tyrosine kinase receptor TrkA is outlined. Finally, the importance of dimeric turn mimics and some new approaches to these are described.
Burgess
K
K
Chemistry Department, Texas A & M University, Box 30012, College Station, Texas 77842-3012, USA.
D006801:Humans; D018716:Molecular Mimicry; D020932:Nerve Growth Factor / Q000737:chemistry / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis*; D019151:Peptide Library; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D020917:Receptor, trkA / Q000737:chemistry / Q000378:metabolism
D009842:Oligopeptides; D019151:Peptide Library; D011506:Proteins; D020932:Nerve Growth Factor; D020917:Receptor, trkA