A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated α-defensins
A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated α-defensins
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DOI：
10.1126/science.286.5439.498
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发表时间：
1999-10-15
期刊：
影响因子：
56.9
通讯作者：
Selsted, ME
中科院分区：
文献类型：
--
作者：
Tang, YQ;Yuan, J;Selsted, ME
恒河猴白细胞的分析揭示了中性粒细胞和单核细胞颗粒中存在18个残基的大环三硫抗生素肽。这种肽被称为恒河猴防御素-1（RTD-1），在低微摩尔浓度下对细菌和真菌具有杀微生物作用。环肽的抗菌活性是开链类似物的三倍，并且在150毫摩尔氯化钠存在下，环构象是抗菌活性所需的。RTD-1的生物合成涉及两个α-防御素相关九肽的首尾连接，需要形成两个新的肽键。因此，宿主防御细胞具有大环抗生素肽的合成和颗粒包装机制，这些大环抗生素肽是吞噬细胞抗微生物装备的组成部分。
Analysis of rhesus macaque leukocytes disclosed the presence of an 18-residue macrocyclic, tridisulfide antibiotic peptide in granules of neutrophils and monocytes. The peptide, termed rhesus theta defensin-1 (RTD-1), is microbicidal for bacteria and fungi at Low micromolar concentrations. Antibacterial activity of the cyclic peptide was threefold greater than that of an open-chain analog, and the cyclic conformation was required for antimicrobial activity in the presence of 150 millimolar sodium chloride. Biosynthesis of RTD-1 involves the head-to-tail ligation of two alpha-defensin-related nonapeptides, requiring the formation of two new peptide bonds. Thus, host defense cells possess mechanisms for synthesis and granular packaging of macrocyclic antibiotic peptides that are components of the phagocyte antimicrobial armamentarium.