Enzymatic synthesis of a new inhibitor of alpha-amylases: acarviosinyl-isomaltosyl-spiro-thiohydantoin

Carbohydr Res. 2005 May 23;340(7):1311-7. doi: 10.1016/j.carres.2005.03.003.

Abstract

Synthesis of acarviosinyl-isomaltosyl-spiro-thiohydantoin in yields up to 20%, has been achieved by Bacillus stearothermophilus maltogenic amylase (BSMA). BSMA is capable of transferring the acarviosine-glucose residue from an acarbose donor onto glucopyranosylidene-spiro-thiohydantoin. Reactions were followed using HPLC and MALDI-TOF MS. 1H and 13C NMR studies revealed that the enzyme reserved its stereoselectivity. Glycosylation took place mainly at C-6 resulting in alpha-acarviosinyl-(1-->4)-alpha-D-glucopyranosyl-(1-->6)-D-glucopyranosylidene-spiro-thiohydantoin. This compound was found to be a much more efficient salivary amylase inhibitor than glucopyranosylidene-spiro-thiohydantoin with kinetic constants of K(EI)=0.19 microM and K(ESI)=0.24 microM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Geobacillus stearothermophilus / enzymology*
  • Glycoside Hydrolases / chemistry*
  • Oligosaccharides / biosynthesis*
  • Oligosaccharides / chemistry
  • Thiohydantoins / chemistry
  • alpha-Amylases / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • Oligosaccharides
  • Thiohydantoins
  • acarviosinyl-isomaltosyl-spiro-thiohydantoin
  • Glycoside Hydrolases
  • alpha-Amylases
  • glucan 1,4-alpha-maltohydrolase