N3-(碘乙酰基)-L-2,3-二氨基丙酸-肽缀合物的抗菌特性

Antimicrobial properties of N3-(iodoacetyl)-L-2,3-diaminopropanoic acid-peptide conjugates.

作者信息

Andruszkiewicz R, Chmara H, Milewski S, Zieniawa T, Borowski E

机构信息

Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, Poland.

出版信息

J Med Chem. 1990 Oct;33(10):2755-9. doi: 10.1021/jm00172a012.

DOI:10.1021/jm00172a012

PMID:2120441

Abstract

Six peptide conjugates consisting of either norvaline, methionine, or lysine and N3-(iodoacetyl)-L-2,3-diaminopropanoic acid--a strong, irreversible inactivator of bacterial and fungal glucosamine-6-phosphate synthase--were synthesized and their antibacterial and antifungal activities were evaluated. Antimicrobial potencies of these peptides were correlated with their transport and cleavage rates inside the cells. Bacteriolysis of Bacillus pumilus cells and inhibition of [14C]glucose incorporation into cell-wall polysaccharides of Candida albicans as a result of glucosamine 6-phosphate inactivation were also observed. Reversal of growth inhibitory effect of these peptides by N-acetylglucosamine in bacteria and fungi suggests the effective delivery of N3-iodoacetyl-L-2,3-diaminopropanoic acid into the cell by a peptide-transport system.

摘要

合成了六种由正缬氨酸、蛋氨酸或赖氨酸与N3-(碘乙酰基)-L-2,3-二氨基丙酸（一种强效、不可逆的细菌和真菌葡糖胺-6-磷酸合酶失活剂）组成的肽缀合物，并评估了它们的抗菌和抗真菌活性。这些肽的抗菌效力与其在细胞内的转运和裂解速率相关。还观察到短小芽孢杆菌细胞的溶菌作用以及由于葡糖胺6-磷酸失活导致的[14C]葡萄糖掺入白色念珠菌细胞壁多糖的抑制作用。N-乙酰葡糖胺对这些肽在细菌和真菌中的生长抑制作用的逆转表明，N3-碘乙酰基-L-2,3-二氨基丙酸通过肽转运系统有效地递送至细胞内。