[Synthesis and anti-Candida albicans properties of L-4-oxalysine-N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic-containing peptide analogues]

Yao Xue Xue Bao. 1998 Jun;33(6):429-35.
[Article in Chinese]

Abstract

In order to improve the inhibitory activity of L-4-oxalysine(abbreviated as I-677) against clinically important pathogen Candida albicans, double-warheads peptide analogues containing I-677 and N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic acid(FMDP) were designed based on the concept of "Illicit Transport" and peptide transport specificities of C. albicans. One compound of I-677-FMDP and seven compounds of I-677-AA-FMDP(AA = Nva, Leu, Val, Phe, Pro, D-Pgly, D, L-p-Cl-Phe) were synthesized and examined for antifungal activities. The results of anti-Candida albicans test in vitro of these double- warheads peptide analogues containing I-677 and FMDP showed very high activities against Candida albicans. The molar MIC (molar minimum inhibitory concentration) ratio of free I-677 to I-677-AA-FMDP is 40-770 and that of FMDP is 60-1130. The values of molar MIC of I-677-AA-FMDP varied from 6.56 x 10(-9) mol.disk-1 to 3.5 x 10(-10) mol.disk-1. The results of competitive antagonism studies indicated that I-677-AA-FMDP were transported into Candida albicans cells by the di-tripeptide permease and subsequently hydrolyzed by intracellular peptidases, releasing free I-677 and FMDP inside cells. The result of antienzymic degradation test in vitro of I-677-FMDP showed that compound I-677-FMDP was resistant to the hydrolysis by carboxypeptidase A.

MeSH terms

  • Animals
  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / pharmacology
  • Candida albicans / drug effects*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Fumarates / chemical synthesis*
  • Fumarates / pharmacology
  • Mice
  • Peptides
  • beta-Alanine / analogs & derivatives*
  • beta-Alanine / chemical synthesis*
  • beta-Alanine / pharmacology

Substances

  • Antifungal Agents
  • Enzyme Inhibitors
  • Fumarates
  • Peptides
  • beta-Alanine
  • N(3)-(4-methoxyfumaroyl)-2,3-diaminopropionic acid