Juba Melanie L, Porter Devin K, Williams Elissa H, Rodriguez Carlos A, Barksdale Stephanie M, Bishop Barney M
Department of Chemistry and Biochemistry, George Mason University, 4400 University Dr., Fairfax, VA 22030, USA.
Department of Chemistry and Biochemistry, George Mason University, 4400 University Dr., Fairfax, VA 22030, USA; Material Measurement Laboratory, National Institute of Science and Technology, 100 Bureau Dr., Gaithersburg, MD 20899, USA.
Biochim Biophys Acta. 2015 May;1848(5):1081-91. doi: 10.1016/j.bbamem.2015.01.007. Epub 2015 Feb 3.
Cationic antimicrobial peptides (CAMPs) are important elements of innate immunity in higher organisms, representing an ancient defense mechanism against pathogenic bacteria. These peptides exhibit broad-spectrum antimicrobial activities, utilizing mechanisms that involve targeting bacterial membranes. Recently, a 34-residue CAMP (NA-CATH) was identified in cDNA from the venom gland of the Chinese cobra (Naja atra). A semi-conserved 11-residue pattern observed in the NA-CATH sequence provided the basis for generating an 11-residue truncated peptide, ATRA-1A, and its corresponding D-peptide isomer. While the antimicrobial and biophysical properties of the ATRA-1A stereoisomers have been investigated, their modes of action remain unclear. More broadly, mechanistic differences that can arise when investigating minimal antimicrobial units within larger naturally occurring CAMPs have not been rigorously explored. Therefore, the studies reported here are focused on this question and the interactions of full-length NA-CATH and the truncated ATRA-1A isomers with bacterial membranes. The results of these studies indicate that in engineering the ATRA-1A isomers, the associated change in peptide length and charge dramatically impacts not only their antimicrobial effectiveness, but also the mechanism of action they employ relative to that of the full-length parent peptide NA-CATH. These insights are relevant to future efforts to develop shorter versions of larger naturally occurring CAMPs for potential therapeutic applications.
阳离子抗菌肽（CAMP）是高等生物先天免疫的重要组成部分，代表了一种对抗病原菌的古老防御机制。这些肽具有广谱抗菌活性，其作用机制涉及靶向细菌膜。最近，在中国眼镜蛇（舟山眼镜蛇）毒腺的cDNA中鉴定出一种由34个氨基酸残基组成的CAMP（NA - CATH）。在NA - CATH序列中观察到的一个半保守的11个氨基酸残基模式为生成一个11个氨基酸残基的截短肽ATRA - 1A及其相应的D - 肽异构体提供了基础。虽然已经研究了ATRA - 1A立体异构体的抗菌和生物物理特性，但其作用方式仍不清楚。更广泛地说，在研究较大的天然存在的CAMP中的最小抗菌单元时可能出现的机制差异尚未得到严格探索。因此，本文报道的研究集中在这个问题以及全长NA - CATH和截短的ATRA - 1A异构体与细菌膜的相互作用上。这些研究结果表明，在设计ATRA - 1A异构体时，肽长度和电荷的相关变化不仅会显著影响它们的抗菌效果，还会影响它们相对于全长母体肽NA - CATH所采用的作用机制。这些见解与未来开发更短版本的较大天然存在的CAMP用于潜在治疗应用的努力相关。
