To design novel antimicrobial peptides by utilizing the sequence of the human host defense protein, chemerin, a seven-residue amphipathic stretch located in the amino acid region, 109–115, was identified, which possesses the highest density of hydrophobic and positively charged residues. Although this 7-mer peptide was inactive toward microorganisms, its 14-mer tandem repeat (Chem-KVL) was highly active against different bacteria including methicillin-resistant Staphylococcus aureus, a multidrug-resistant Staphylococcus aureus strain, and slow- and fast-growing mycobacterial species. The selective enantiomeric substitutions of its two l-lysine residues were attempted to confer cell selectivity and proteolytic stability to Chem-KVL. Chem-8dK with a d-lysine replacement in its middle (eighth position) showed the lowest hemolytic activity against human red blood cells among Chem-KVL analogues and maintained high antimicrobial properties. Chem-8dK showed in vivo efficacy against Pseudomonas aeruginosa infection in BALB/c mice and inhibited the development of resistance in this microorganism up to 30 serial passages and growth of intracellular mycobacteria in THP-1 cells.

中文翻译：

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一种短的人类 Chemerin 衍生肽的串联重复及其无毒的含 d-赖氨酸的对映异构体显示出广谱抗菌和抗结核活性

为了利用人类宿主防御蛋白 chemerin 的序列设计新型抗菌肽，鉴定了位于氨基酸区域 109-115 的七残基两亲性片段，其具有最高密度的疏水性和正电荷残基。尽管这种 7 聚体肽对微生物无活性，但其 14 聚体串联重复序列 (Chem-KVL) 对不同细菌具有高度活性，包括耐甲氧西林金黄色葡萄球菌、耐多药金黄色葡萄球菌菌株以及生长缓慢和快速的葡萄球菌分枝杆菌种。尝试对其两个l-赖氨酸残基的选择性对映体置换赋予 Chem-KVL 细胞选择性和蛋白水解稳定性。Chem-8dK 与在 Chem-KVL 类似物中，d-赖氨酸替代物在其中间（第八位）显示出对人红细胞的最低溶血活性，并保持高抗菌性能。Chem-8dK在 BALB/c 小鼠中显示出抗铜绿假单胞菌感染的体内功效，并抑制该微生物的耐药性发展，最多可连续传代 30 次，并抑制 THP-1 细胞中细胞内分枝杆菌的生长。