Synthesis and Anti-Elastase Activity of Amide-Cyclized Peptide Analogs of Alpha1-Antitrypsin,
WATERLOO UNIV (ONTARIO)
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The serine protease inhibitor a1-antitrypsin is the most potent inhibitor of human leukocyte elastase HLE. The mechanism of inhibition of HLE by a 1-AT has not been clearly defined. We have synthesized linear and side-chain cyclized peptide analogs of the reactive site region of this natural inhibitor in an attempt to mimic its bioactive conformation. The alpha-AT analogs 1-3 enclose the reactive site within a loop defined by an amide bond between glutamic acid and lysine side chains, while peptides are cyclized to stabilize either an alpha-helix or a bend in the enzyme binding region N-terminal to the reactive site.