THE DESIGN, SYNTHESIS AND STUDY OF SIDEROPHORE-ANTIBIOTIC CONJUGATES - SIDEROPHORE MEDIATED DRUG TRANSPORT

被引:25
作者
MILLER, MJ
MCKEE, JA
MINNICK, AA
DOLENCE, EK
机构
[1] Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, 46556, Indiana
来源
BIOLOGY OF METALS | 1991年 / 4卷 / 01期
关键词
SIDEROPHORE; IRON TRANSPORT; ANTIBIOTIC; BETA-LACTAM;
D O I
10.1007/BF01135559
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The use of conjugates of microbial iron chelators (siderophores) and antibiotics for illicit transport of antibiotics into cells is a potentially powerful method for the rational design of therapeutic agents. The structural complexity of most natural siderophores has impeded progress in this area. Described here are the design, syntheses and preliminary biological studies of several siderophore-β-lactam antibiotic conjugates. Both hydroxamic-acid-based and catechol-based conjugates with and without amino acid spacers to carbacephalosporins were synthesized and demonstrated to be effective inhibitors of Escherichia coli X580. Mutant selection was noted for each class of conjugates. Mutants selected from exposure of the E. coli to the hydroxamate conjugates were susceptible to the catechol conjugates and vice versa. Combinations of hydroxamate-and catechol-carbacephalosporin conjugates were most effective inhibitors of E. coli X580. © 1991 Springer-Verlag.
引用
收藏
页码:62 / 69
页数:8
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