Antifungal activity of a Candida albicans GGTase I inhibitor-alanine conjugate. Inhibition of Rho1p prenylation in C. albicans

Bioorg Med Chem Lett. 2003 Jun 2;13(11):1935-7. doi: 10.1016/s0960-894x(03)00320-2.

Abstract

An alanine conjugate of a Candida albicans geranylgeranyl transferase I inhibitor was synthesized to facilitate its uptake into the fungal cell. The antifungal activity of CaGGTase-Ala conjugate is demonstrated. It is also shown that the CaGGTase-Ala conjugate affects prenylation of endogenous Rho1p, but has no effect on prenylation of endogenous Ras1p.

MeSH terms

  • Alanine / analogs & derivatives*
  • Alanine / chemical synthesis
  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry*
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects
  • Candida albicans / enzymology*
  • Cells, Cultured
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Fungal Proteins / antagonists & inhibitors
  • Microbial Sensitivity Tests
  • Oligonucleotides / chemical synthesis
  • Oligonucleotides / chemistry
  • Oligonucleotides / pharmacology
  • Protein Prenylation / drug effects
  • rho GTP-Binding Proteins / antagonists & inhibitors
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Antifungal Agents
  • Enzyme Inhibitors
  • Fungal Proteins
  • Oligonucleotides
  • Alkyl and Aryl Transferases
  • geranylgeranyltransferase type-I
  • rho GTP-Binding Proteins
  • Alanine