The synthesis of azapeptidomimetic beta-lactam molecules as potential protease inhibitors.
Synthetic methods for the construction of a novel peptidomimetic structure are reported. The structure incorporates a beta-lactam and an azapeptide in a peptide backbone with the intention of generating rationally designed substrate-based protease inhibitors. The beta-lactam is formed by subjecting serine or threonine-azapeptides to Mitsunobu reaction conditions. Importantly, the azapeptidomimetic beta-lactam structure permits extended binding inhibition and the synthetic methods to create tetrapeptidomimetic structures are described.
Malachowski
William P
WP
Department of Chemistry and Physics, The University of New England, Biddeford, Maine 04005, USA.
Tie
Chenyang
C
Wang
Katherine
K
Broadrup
Robert L
RL
D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D001372:Aza Compounds; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D047090:beta-Lactams