含L-4-氧代赖氨酸寡肽的合成及其抗白念珠菌活性

本文运用“违法传送”概念,根据白念珠菌对寡肽的传送特点,设计并合成了十个含L-4-氧代赖氨酸(以下称I-677)的寡肽,以提高I-677的抗白念珠菌活性。体外抗白念珠菌试验表明:I-677-肽(I-677-X₁,I-677-X₁-X₂和I-677-X₁-X₂-Gly,其中X₁,X₂=Met,Leu,Ile,Ala,β-Ala,Gly)较I-677单体摩尔活性提高了2.1～28倍,其摩尔最低抑菌浓度为8.7×10^-8～9.3×10^-9mol/ml,传送肽和赖氨酸分别逆转I-677-肽抗菌活性的实验结果证实了I-677的“违法传送”途径。

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.