对抗菌和抗肿瘤具有较高选择性的肽段的设计

2012-02-27 17:23 来源:丁香园 作者:中国石油大学重质油加工国家重点实验室
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Biomacromolecules 2011 Nov;12 (11): 3839-43. [IF:5.325]  
Designed antimicrobial and antitumor peptides with high selectivity.
Hu J , Chen C , Zhang S , Zhao X , Xu H , Zhao X , Lu JR .
State Key Laboratory of Heavy Oil Processing and the Centre for Bioengineering and Biotechnology, China University of Petroleum (East China) , Qingdao 266555, P. R. China.
中国石油大学重质油加工国家重点实验室,中国石油大学生物工程与技术中心

Abstract
We report a new class of cationic amphiphilic peptides with short sequences, G(IIKK)(n)I-NH(2) (n = 1-4), that can kill Gram-positive and Gram-negative bacteria as effectively as several well-known antimicrobial peptides and antibiotics. In addition, some of these peptides possess potent antitumor activities against cancer cell lines. Moreover, their hemolytic activities against human red blood cells (hRBCs) remain remarkably low even at some 10-fold bactericidal minimum inhibitory concentrations (MICs). When bacteria or tumor cells are cocultured with NIH 3T3 fibroblast cells, G(IIKK)(3)I-NH(2) showed fast and strong selectivity against microbial or tumor cells, without any adverse effect on NIH 3T3 cells. The high selectivity and associated features are attributed to two design tactics: the use of Ile residues rather than Leu and the perturbation of the hydrophobic face of the helical structure with the insertion of a positively charged Lys residue. This class of simple peptides hence offers new opportunities in the development of cost-effective and highly selective antimicrobial and antitumor peptide-based treatments.

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