SYNTHESIS AND SIDEROPHORE AND ANTIBACTERIAL ACTIVITY OF N5-ACETYL-N5-HYDROXY-L-ORNITHINE-DERIVED SIDEROPHORE BETA-LACTAM CONJUGATES - IRON-TRANSPORT-MEDIATED DRUG DELIVERY
SYNTHESIS AND SIDEROPHORE AND ANTIBACTERIAL ACTIVITY OF N5-ACETYL-N5-HYDROXY-L-ORNITHINE-DERIVED SIDEROPHORE BETA-LACTAM CONJUGATES - IRON-TRANSPORT-MEDIATED DRUG DELIVERY
复制标题
n5-acetyl-n5-hydroxy-l-ornithine-derived siderophore beta-lactam conjugates 的合成、嗜酸性物质和抗菌活性--铁传输介导的药物输送
DOI：
10.1021/jm00107a014
复制
发表时间：
1991-03-01
影响因子：
7.3
通讯作者：
PAYNE, SM
中科院分区：
文献类型：
--
作者：
DOLENCE, EK;MINNICK, AA;PAYNE, SM
N5-乙酰基-N5-羟基-L-鸟甲基-N5-乙酰基-N5-羟基-L-鸟甲基-N5-乙酰基-N5-羟基-L-鸟氨酸，白霉素和铁色素的功能性工具组分，已作为“载体"亚结构掺入碳青霉菌素和恶嗪型β-内酰胺抗生素中。 将先前合成的该三肽的保护形式（14）与各种β-内酰胺类似物17、19、24和25偶联，得到保护的缀合物21、22、26和27。 通过氢解的最终脱保护提供脱保护的铁载体-β-内酰胺抗生素缀合物1-4。 用铁载体缺陷型福氏志贺菌SA 100或S.福氏SA 240（SA 100 iucD：Tn 5）。 使用两个同基因大肠杆菌菌株的生长促进活性的测量不同的只有在存在或不存在的fhuA（异羟肟酸铁色素受体）表明摄取的异羟肟酸铁转运系统。 这些共轭物的抗菌活性进行了研究，并讨论了潜在的使用的铁铬铁运输系统作为一种手段的药物输送。
N5-Acetyl-N5-hydroxy-L-ornithyl-N5-acetyl-N5-hydroxy-L-ornithyl-N5-acetyl-N5-hydroxy-L-ornithine, the functionally instrumental component of the albomycins and ferrichromes, has been incorporated as a ''carrier'' substructure into both carbacephalosporin and oxamazin type beta-lactam antibiotics. The previously synthesized protected version of this tripeptide (14) was coupled with various beta-lactam analogues 17, 19, 24, and 25 to give protected conjugates 21, 22, 26, and 27. Final deprotection by hydrogenolysis provided the deprotected siderophore-beta-lactam antibiotic conjugates 1-4. The growth-promoting ability of each has been evaluated using either the siderophore-deficient mutant Shigella flexneri SA 100 or S. flexneri SA240 (SA 100 iucD:Tn5). Measurement of the growth-promoting activity using two isogenic Escherichia coli strains differing only in the presence or absence of fhuA (hydroxamate ferrichrome receptor) suggests uptake by the hydroxamate iron-transport system. The antibacterial activity of these conjugates has been investigated, and the potential for use of the ferrichrome iron-transport system as a means of drug delivery is discussed.