On resin amino acid side chain attachment strategy for the head to tail synthesis of new glutamine containing gramicidin-S analogs and their antimicrobial activity.
On resin amino acid side chain attachment strategy for the head to tail synthesis of new glutamine containing gramicidin-S analogs and their antimicrobial activity.
复制标题
关于头尾合成含有短杆菌肽-S类似物的新型谷氨酰胺的树脂氨基酸侧链连接策略及其抗菌活性。
DOI：
10.1016/j.bmcl.2010.08.015
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发表时间：
2010
影响因子：
2.7
通讯作者：
Nefzi,Adel
中科院分区：
文献类型：
--
作者：
Derbal,Safa;Hensler,Mary;Fang,Weiqin;Nizet,Victor;Ghedira,Kamel;Nefzi,Adel
包括耐甲氧西林金黄色葡萄球菌在内的多种耐药细菌引起的感染惊人地增加，促使人们迫切地寻找新的抗菌剂。增加具有抗菌活性的全新支架的发现是旨在修饰现有分子以优化活性或降低毒性的努力。本文报道了利用氨基酸侧链附着策略平行固相合成阳离子抗菌肽gramicidin S （GS）的类似物。鸟氨酸（Orn）残基被谷氨酰胺（Gln）取代，芳香d-苯丙氨酸（Phe）被不同的芳香d-氨基酸取代。另外还合成了含有疏水氨基酸缬氨酸和亮氨酸所有可能组合的GS类似物的谷氨酰胺。在这项工作中，我们还报告了这些类似物对几种临床重要的耐药革兰氏阳性和革兰氏阴性病原体的抗菌活性。
The alarming increase in infections caused by multiple drug resistant bacteria including methicillin-resistant Staphylococcus aureus has prompted a desperate search for new antimicrobials. Augmenting the discoveries of completely new scaffolds with antimicrobial activity are efforts aimed at modifying existing molecules to optimize activity or reduce toxicity. We report herein the parallel solid-phase synthesis of analogues of the cationic antimicrobial peptide gramicidin S (GS) using amino acid side chain attachment strategy. The ornithine (Orn) residues were replaced by glutamine (Gln) and the aromatic d-phenylalanine (Phe) were replaced by different aromatic d-amino acids. Additional Gln containing GS analogues with all the possible combinations of the hydrophobic amino acids valine and leucine were also synthesized. In this work we also report the antibacterial activity of these analogs against several clinically-important drug-resistant Gram-positive and Gram-negative pathogens.