NMR based structure-activity relationship analysis of an antimicrobial peptide, thanatin, engineered by site-specific chemical modification: Activity improvement and spectrum alteration
NMR based structure-activity relationship analysis of an antimicrobial peptide, thanatin, engineered by site-specific chemical modification: Activity improvement and spectrum alteration
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DOI：
10.1016/j.bbrc.2008.02.057
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发表时间：
2008-05-02
影响因子：
3.1
通讯作者：
Taguchi, Selichi
中科院分区：
文献类型：
--
作者：
Imamura, Tomohiro;Yamamoto, Naoki;Taguchi, Selichi
通过在形成分子内二硫桥的两个半胱氨酸残基上用叔丁基进行位点特异性化学修饰，抗菌肽 Thanatin 的活性比天然原始肽高出 4 倍。化学修饰的thanatin (C11tBu/C18tBu) 对革兰氏阳性菌、藤黄微球菌的抗菌活性提高，而对革兰氏阴性菌、大肠杆菌的抗菌活性降低。这一发现表明，二硫键的形成不仅是thanatin发挥抗菌活性所不可缺少的，而且与对细菌的活性特异性密切相关。 NMR 分析表明，thanatin 利用其 C 端 β-发夹结构立体特异性地对抗大肠杆菌，而对抗藤黄杆菌的活性与结构无关，与侧链疏水性密切相关。 (c) 2008 Elsevier Inc. 保留所有权利。
Activity improvement of an antimicrobial peptide, thanatin, has been achieved up to 4-fold higher than natural original one by site-specific chemical modifications with tert-butyl group at two cysteine residues which form an intramoleular disulfide bridge. The chemically modified thanatin (C11tBu/C18tBu) exhibited improved antimicrobial activity toward Gram-positive bacteria, Micrococcus luteus, whereas lowered activity toward Gram-negative bacteria, Escherichia coli. This finding suggests that disulfide-bridge formation is not only indispensable for exhibition of antimicrobial activity of thanatin but also closely related to the activity specificity towards bacteria. NMR analysis indicates that thanatin acts against Ecoli stereospecifically by taking advantage of its C-terminal beta-hairpin structure, while the activity against M. luteus does not relate to structures and correlates very well to side-chain hydrophobicity. (c) 2008 Elsevier Inc. All rights reserved.