Tendamistat (HOE 467), a tight‐binding α‐amylase inhibitor from Streptomyces tendae 4158: Isolation, biochemical properties

Abstract

Culture fluids of Streptomyces tendae 4158 (ATCC 31210) contain a new kind of polypeptide α‐amylase inhibitor. tendamistat (HOE 467). Several methods of isolating this inhibitor are described, including two rapid crystallisation methods, which produce homogeneous material. A characteristic of tendamistat is its tight‐binding, pH‐independent inhibition kinetics and the specific inhibition of the mammalian α‐amylases. The inhibitor and the α‐amylase form a stoichiometric 1:1 complex, which cannot be separated into its individual components by sodium dodecyl sulphate or molecular sieve chromatography. Studies of the mode of action reveal that the α‐amylase‐inhibiting activity is linked to the intact disulphide bridges of the inhibitor. It is assumed that the multipoint protein‐protein bond exists between the enzyme and tendamistat. It is shown that extracellular tendamistat inhibits amylase formed by streptomyces. We therefore assume a regulatory function in the microorganism. By‐products of tendamistat, which possess similar enzyme‐inhibiting properties, are also described. Copyright © 1984, Wiley Blackwell. All rights reserved