Antimicrobial activity of the Naja atra cathelicidin and related small peptides

Antimicrobial activity of the Naja atra cathelicidin and related small peptides
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DOI:
10.1016/j.bbrc.2010.04.158
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发表时间:
2010-06-11
影响因子:
3.1
通讯作者:
van Hoek, Monique L.
van Hoek, Monique L.
中科院分区:
生物学4区
文献类型:
--
作者:
de Latour, Frank A.;Amer, Lilian S.;van Hoek, Monique L.

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我们在中国眼镜蛇 (Naja atra) cathelicidin 的序列中鉴定了一个 11 残基模式 (KR(F/A)KKFFKK(L/P)K),我们将其命名为 ATRA 基序。设计了一系列 11 残基肽(ATRA-1、-2、-1A 和 -1P)来探讨 ATRA 基序内保守残基的重要性及其对抗菌性能的贡献。评估了这些肽针对大肠杆菌 K12 菌株和放线菌聚合菌 Y4 的抗菌活性。 ATRA-1 和-1A 的效力与 N. atra cathelicidin 相当。通过圆二色性对四种短肽进行的结构检查表明了基序内特定氨基酸位置对螺旋性的贡献的重要性。这些研究的结果表明,源自 N. atra cathelicidin 的重复 ATRA 基序的短肽可以表现出对宿主细胞的低毒性和对本研究中使用的革兰氏阴性菌的高抗菌活性。它们构成了新型、有效的抗菌肽,比天然抗菌肽更短(因此生产成本更低),并且它们可能代表治疗药物开发的新模板。 (c) 2010 Elsevier Inc. 保留所有权利。
We have identified an 11-residue pattern (KR(F/A)KKFFKK(L/P)K), which we have named the ATRA motif, within the sequence of the Chinese cobra (Naja atra) cathelicidin. A series of 11-residue peptides (ATRA-1, -2, -1A and -1P) were designed to probe the significance of the conserved residues within the ATRA motif, and their contributions to antimicrobial performance. The antimicrobial activities of the peptides were assessed against Escherichia coli K12 strain and Aggregatibacter actinomycetemcomitans Y4. ATRA-1 and -1A, demonstrated potencies comparable to that of N. atra cathelicidin. Structural examination by circular dichroism of the four short peptides suggested the significance of specific amino acid positions within the motif by their contribution to helicity. The results of these studies indicate that short peptides derived from the repeated ATRA motif from the N. atra cathelicidin can demonstrate both low toxicity against host cells and high antimicrobial activity against the gram-negative bacteria used in this study. They constitute novel, effective antimicrobial peptides that are much shorter (and thus less expensive to produce) than the natural cathelicidins, and they may represent new templates for therapeutic drug development. (c) 2010 Elsevier Inc. All rights reserved.