Phosphinate, sulfonate, and sulfonamidate dipeptides as potential inhibitors of Escherichia coli aminopeptidase N

Bioorg Med Chem Lett. 2005 Dec 1;15(23):5150-3. doi: 10.1016/j.bmcl.2005.08.055. Epub 2005 Sep 15.

Abstract

In an effort to prepare novel inhibitors of bacterial aminopeptidase N (PepN), the phosphinate, propenylphosphinate, decylphosphinate, sulfonate, and sulfonamidate analogs of Ala-Ala were synthesized and tested as inhibitors. Phosphinate 1 was shown to inhibit PepN with a K(i) of 10microM, and propenylphosphinate 2 and decylphosphinate 3 inhibited PepN with a K(i) of ca. 1microM. Sulfonate and sulfonamidate analogs did not inhibit PepN.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aminopeptidases / antagonists & inhibitors*
  • Bacterial Proteins / antagonists & inhibitors*
  • Dipeptides / chemistry*
  • Escherichia coli / enzymology*
  • Phosphinic Acids / chemistry
  • Phosphinic Acids / pharmacology
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology
  • Sulfonic Acids / chemistry
  • Sulfonic Acids / pharmacology

Substances

  • Bacterial Proteins
  • Dipeptides
  • Phosphinic Acids
  • Protease Inhibitors
  • Sulfonamides
  • Sulfonic Acids
  • pepN protein, Bacteria
  • alanylalanine
  • Aminopeptidases