SYNTHESIS AND ANTI-CANDIDA ALBICANS ACTIVITY OF L-4-OXALYSINE-CONTAINING OLIGOPEPTIDES

In order to improve the inhibitory activity of L-4-oxalysine (designated as Ⅰ-677) against clinical important pathogen Candid. albicans, ten oligopeptides containing Ⅰ-677, Ⅰ-677-Ⅹ₁, Ⅰ-677-Ⅹ₁-Ⅹ₂, Ⅰ-677-Ⅹ₁-Ⅹ₂-GIy (Ⅹ₁, Ⅹ₂=Met, Leu, Ile, Ala, β-Ala and Gly)were designed and synthesized according to the concept of "Illicit Transport" and peptide transport specifieities of C. albieans. Anti-Candida albicans test in vitro Showed that these Ⅰ-677-peptides had higher activities determined as molar minimum inhibitory concentrations (molar MIC)than that of free Ⅰ-677 by 2.1 to 28-fold. The values of molar MIC varied from 8.7× 10^(-8) to 9.3×10^-9mol/ml. The results of antagonism tests in which Gly-Gly or Lysine can reverse the antimicrobial activities of Ⅰ-677-Leu supported the way of "Illicit Transport" of Ⅰ-677 within which peptide permease of microorganisms mediated the entry of Ⅰ-677-peptide into the cells, followed by the enzymatic release of free Ⅰ-677 inside the cells.The mixed anhydride and active ester condensation procedures in homogeneous solution were carried out for the peptide synthesis and the MIC were determined by the disk diffusion assay.