Peptide inhibitors of alpha-amylase based on tendamistat:synthesis and kinetic studies

摘要

Tendamistat is a tight-binding pseudo-irreversible inhibitor of mammalian alpha-amylases with a KI value of 9·10~(-12)M.The crystal structure of the alpha-amylase-Tendamistat complex has been elucidated by X-ray techniques and nuclear magnetic resonance spectroscopy,revealing that only 15 of the 74 amino acids in the inhibitor (in 4 segments,shown below) actually interact directly with the enzyme binding site via hydrogen bonding and hydrophobic and electrostatic forces.Our goal was to design smaller analogs of Tendamistat,which might be less immunogenic.