SYNTHETIC BACTERICIDAL PEPTIDE-BASED ON CAP37 - A 37-KDA HUMAN NEUTROPHIL GRANULE-ASSOCIATED CATIONIC ANTIMICROBIAL PROTEIN CHEMOTACTIC FOR MONOCYTES
SYNTHETIC BACTERICIDAL PEPTIDE-BASED ON CAP37 - A 37-KDA HUMAN NEUTROPHIL GRANULE-ASSOCIATED CATIONIC ANTIMICROBIAL PROTEIN CHEMOTACTIC FOR MONOCYTES
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DOI：
10.1073/pnas.90.10.4733
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发表时间：
1993-05-15
影响因子：
11.1
通讯作者：
SPITZNAGEL, JK
中科院分区：
文献类型：
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作者：
PEREIRA, HA;ERDEM, I;SPITZNAGEL, JK
CAP 37（分子量为37 kDa的阳离子抗菌蛋白）是从人中性粒细胞颗粒中分离的多功能蛋白。它具有抗生素和趋化性，并结合脂多糖。基于CAP 37蛋白的残基20-44的合成肽，氨基酸序列NQGRHFCGGALIHARFVMTAASCFQ，模拟其抗生素和脂多糖结合作用。肽20-44在测试浓度下对鼠伤寒沙门氏菌、铜绿假单胞菌、大肠杆菌、粪肠球菌和金黄色葡萄球菌具有抗菌活性。该肽的杀菌作用是pH依赖性的，在pH 5.0和pH 5.5时具有最大活性，在pH 7.0时活性降低。序列中的各种截短、取代和其他修饰使其活性劣化。游离巯基和/或二硫桥的形成是最佳抗生素活性所必需的，因为丝氨酸取代或烷基化半胱氨酸残基26和42消除了杀菌活性。显然，氨基酸20-44代表CAP 37的重要的、可能是主要的抗菌结构域。这种肽应该为CAP 37的抗微生物活性机制提供新的见解，并可能作为新的有用的合成抗生素的模型。
CAP37 (cationic antimicrobial protein of molecular mass 37 kDa) is a multifunctional protein isolated from the granules of human neutrophils. It is antibiotic and chemotactic and binds lipopolysaccharide. A synthetic peptide, amino acid sequence NQGRHFCGGALIHARFVMTAASCFQ, based on residues 20-44 of CAP37 protein mimics its antibiotic and lipopolysaccharide binding action. Peptide 20-44, at the concentrations tested, has antibacterial activity against Salmonella typhimurium, Pseudomonas aeruginosa, Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus. The bactericidal action of the peptide was pH dependent, with maximum activity at pH 5.0 and pH 5.5 and decreased activity at pH 7.0. Various truncations, substitutions, and other modifications in the sequence deteriorate its activity. Free sulfhydryl groups and/or disulfide bridge formation are required for optimum antibiotic activity, since substitution of serines for, or alkylation of, cysteine residues 26 and 42 eliminates bactericidal activity. Evidently amino acids 20-44 represent an important, perhaps principal, antibacterial domain of CAP37. This peptide should provide new insight into the mechanism of antimicrobial activity of CAP37 and may serve as a model for new, useful, synthetic antibiotics.