Peptide inhibitors of alpha-amylase based on tendamistat: development of analogues with omega-amino acids linking critical binding segments

Protein Pept Lett. 2005 Apr;12(3):275-80. doi: 10.2174/0929866053587110.

Abstract

Peptide analogues of Tendamistat which include the most essential residues linked by novel omega-amino acids (X,Y,Z: H2N-(CH2)n-CO(2)H, where n=2-10) were designed, synthesized (Ac-Tyr(15)-X-Trp(18)-Arg(19)-Tyr(20)-Y-Thr(55)-Z-Asp(58)-Gly(59)-Tyr(60)-Ile(61)-Gly(62)-NH2), and analyzed for alpha-amylase inhibitory activity. Native dipeptide spacers sometimes were left intact at X and Z. Analogues demonstrated competitive inhibition with K(i) values ranging from 23 to 767 microM. 8-Aminooctanoic acid was the optimal linker at Y, while longer linkers were favored at the other positions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Humans
  • Molecular Structure
  • Peptides* / chemical synthesis
  • Peptides* / chemistry*
  • Peptides* / metabolism
  • Protein Binding
  • alpha-Amylases / antagonists & inhibitors*
  • alpha-Amylases / metabolism

Substances

  • Amino Acids
  • Enzyme Inhibitors
  • Peptides
  • alpha-Amylases
  • tendamistate