Park Yoonkyung, Hahm Kyung-Soo
Research Center for Proteineous Materials, Chosun University, Gwangju 501-759, Korea.
Protein Pept Lett. 2012 Jun 1;19(6):652-6. doi: 10.2174/092986612800494093.
In a previous study, we reported that truncation of HP (2-20) (derived from the N-terminal region of Helicobacter pylori Ribosomal Protein L1 (RPL1)) at the N- (residues 2-3) and C-terminal (residues 17-20) truncated fragments to give HP (4-16) induces increased antibiotic activity against several bacterial strains without hemolysis. In this study, to develop novel short antibiotic peptides useful as therapeutic drugs, an analogue was designed to possess increased hydrophobicity by Trp substitution in position 2 region of HP (4-16). Synthetic HP (4-16)-W showed an enhanced antimicrobial and antitumor activity. The antimicrobial activity of this peptide and others was measured by their growth inhibitory effect upon S. aureus, B. subtilis, S. epidermidis, E. coli, S. typimurium, P. aeruginosa, C. albicans, T. beigelii and S. cerevisiae. None of the peptides exhibited hemolytic activity against human erythrocyte cells except melittin as a positive control. Its antibiotic activity suggests that HP (4-16)-W is an excellent candidate as a lead compound for the development of novel antibiotic agents.
在先前的一项研究中，我们报道了幽门螺杆菌核糖体蛋白L1（RPL1）N端区域衍生的HP（2-20）在N端（第2-3位残基）和C端（第17-20位残基）截短得到HP（4-16）后，对几种细菌菌株的抗生素活性增强且无溶血现象。在本研究中，为开发用作治疗药物的新型短抗生素肽，设计了一种类似物，通过在HP（4-16）的第2位区域进行色氨酸取代来增加疏水性。合成的HP（4-16）-W显示出增强的抗菌和抗肿瘤活性。通过它们对金黄色葡萄球菌、枯草芽孢杆菌、表皮葡萄球菌、大肠杆菌、鼠伤寒沙门氏菌、铜绿假单胞菌、白色念珠菌、贝氏隐球菌和酿酒酵母的生长抑制作用来测定该肽及其他肽的抗菌活性。除作为阳性对照的蜂毒素外，这些肽均未对人红细胞表现出溶血活性。其抗生素活性表明HP（4-16）-W是开发新型抗生素药物的先导化合物的极佳候选物。
