Synthesis and solution structure of the antimicrobial peptide protegrin-1
Synthesis and solution structure of the antimicrobial peptide protegrin-1
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DOI：
10.1111/j.1432-1033.1996.0575p.x
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发表时间：
1996-05-01
期刊：
影响因子：
--
通讯作者：
Chavanieu, A
中科院分区：
文献类型：
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作者：
Aumelas, A;Mangoni, M;Chavanieu, A
蛋白蛋白是最近从猪细胞中分离出来的富含cys的阳离子抗菌肽家族的5个成员。我们合成了一个18个氨基酸的肽，与蛋白蛋白1相对应。经过Cys氧化后，肽对革兰氏阳性和革兰氏阴性细菌具有杀菌活性，与天然肽相似。采用h -1核磁共振波谱法研究了蛋白蛋白-1在水和（CD3）(2)SO中的溶液结构，并进行了距离几何和模拟退火计算。C6-C15和C8-C13二硫化物模式是在核磁共振衍生约束的基础上确定的。这两个平行的二硫化物桥稳定了由两个反平行链（残基5-9和12-16）组成的β片结构，该结构由扭曲的β转（残基9-12）连接。n端和c端基本上是无序的。疏水和亲水残基在肽表面的分布被发现是与tachyplesin-1（一种具有细胞溶解活性的相关肽）共享的结构特征，并且在较小程度上与哺乳动物防御素共享。这些发现使我们假设这种分布模式可能是这些肽的细胞溶解活性所必需的。
Protegrins are members of a family of five Cys-rich, cationic antimicrobial peptides recently isolated from porcine cells. We have synthesised an 18-amino-acid peptide that corresponds to protegrin-1. After Cys oxidation, the peptide has bactericidal activity against gram-positive and gram-negative bacteria, similar to that described for the natural peptide. The solution structure of protegrin-1 was investigated by means of H-1-NMR spectroscopy in water and in (CD3)(2)SO, with distance-geometry and simulated-annealing calculations. The C6-C15 and C8-C13 disulfide pattern was determined on the basis of NMR-derived constraints. These two parallel disulfide bridges stabilised a beta-sheet structure which comprised two antiparallel strands (residues 5-9 and 12-16) linked by a distorted beta-turn (residues 9-12). The N-terminus and C-terminus were essentially disordered. The distribution of hydrophobic and hydrophilic residues at the peptide surface was found to be a structural feature shared with tachyplesin-1, a related peptide which displays cytolytic activity, and, to a lesser extent, with mammalian defensins. These findings led us to assume that the distribution pattern could be required for the cytolytic activity of these peptides.