Emerging trends in macromolecular antimicrobials to fight multi-drug-resistant infections

被引:307
作者
Engler, Amanda C. [1 ]
Wiradharma, Nikken [2 ]
Ong, Zhan Yuin [2 ]
Coady, Daniel J. [1 ]
Hedrick, James L. [1 ]
Yang, Yi-Yan [2 ]
机构
[1] IBM Almaden Res Ctr, San Jose, CA 95120 USA
[2] Inst Bioengn & Nanotechnol, Singapore 138669, Singapore
关键词
Antimicrobial; Macromolecule; Polymer; Self-assembly; Peptide; Dendrimer; DE-NOVO DESIGN; BIOLOGICALLY-ACTIVE POLYCATIONS; HOST-DEFENSE PEPTIDES; HEMOLYTIC ACTIVITIES; ANTIBACTERIAL ACTIVITIES; QUATERNARY AMMONIUM; AMINO-ACID; MEMBRANE-BINDING; CANDIDA-ALBICANS; SELF-ASSOCIATION;
D O I
10.1016/j.nantod.2012.04.003
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Synthetic macromolecular antimicrobials are a highly promising class of therapeutics with immense potential for combating multidrug resistant microbes. In contrast to conventional small molecule antibiotics, macromolecular antimicrobial agents mediate physical disruption of microbial cell membranes, thereby reducing the likelihood of pathogens developing resistance. This review highlights recent advances in the development of synthetic membrane-active macromolecules with focus on peptides and polymers that adopt well-defined nanostructures or conformations (e.g. secondary helical structures, self-assembled nanoparticles, and hyperbranched structures). An overview of proposed antimicrobial mechanisms, followed by a description of structural parameters which govern selectivity of macromolecular agents for microbial cells over mammalian cells is provided. Pertinent examples of well-defined nanostructure-based macromolecular antimicrobial agents are discussed. Moreover, challenges and future perspectives in the development of safe and effective macromolecular antimicrobial agents for eventual clinical applications are presented. (C) 2012 Published by Elsevier Ltd.
引用
收藏
页码:201 / 222
页数:22
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