Nonhemolytic abiogenic polymers as antimicrobial peptide mimics
Nonhemolytic abiogenic polymers as antimicrobial peptide mimics
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DOI：
10.1002/pola.20304
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发表时间：
2004-08-01
影响因子：
--
通讯作者：
Tew, GN
中科院分区：
文献类型：
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作者：
Arnt, L;Nüsslein, K;Tew, GN
开发新的抗微生物化合物和材料的新方法仍然是一个重要的研究领域。已经报道了许多不同的设计，包括将已知的抗生素如环丙沙星、1 N-卤胺、2，3和2，4二氯苯基4，5掺入聚合物中的设计。6，7或者，阳离子聚合物，已经受到相当大的关注，8是众所周知的消毒剂，包括聚赖氨酸，9季铵盐，10吡啶盐，7，8聚胍，11和聚双胍。同时，宿主防御肽代表了一大组具有广谱抗微生物活性的天然化合物，它们也在细菌细胞和哺乳动物红细胞（RBC）之间显示出选择性。宿主防御肽的实例包括-螺旋爪蟾抗菌肽和天蚕抗菌肽，以及含有-链的防御素。它们引起了许多研究人员的注意，并且对其基本理化性质和作用模式有了重要的了解。13-16这些肽破坏磷脂膜的能力，最终杀死细胞，被认为来自于采用表面两亲性（FA）结构。因此，整体结构，而不是精确的化学组成或氨基酸序列，是至关重要的。这意味着模拟FA结构应该提供具有类似生物化学性质的合成分子，从而产生相对简单的聚合物，这些聚合物是有效的抗微生物剂并且无毒，但价格低廉且易于制备。最近报道了基于合成肽和类肽的两亲性螺旋结构，其模拟爪蟾抗菌肽的整体结构和活性。20-26合成了具有相同净电荷的一系列肽;然而，取代模式是不同的。21，23，24确定最具活性的肽是具有最高程度的表面两亲性的那些。因此，可以得出结论，该结构对于抗菌活性和选择性是必要的，这与先前从合成肽的发现一致。23，24此外，生物学中对FA结构的广泛观察，从肽到类固醇，27暗示了这种结构的重要性。这些聚酰胺实例模拟了天然宿主防御肽的螺旋结构和阳离子性质。此外，这些模拟物是通过固相技术制备的离散化合物，需要大量的努力和昂贵的纯化。将基本理化性质转移到简单聚合物的能力将为各种应用提供快速，廉价的分子，包括医疗涂层，抗菌管和其他材料。作为非生物宿主防御肽模拟物的聚合物系统的初步工作是用芳基酰胺主链进行的。这些系统被设计成模拟宿主防御肽的基本结构和生理化学性质，但不是螺旋结构。它们对几种细菌菌株的活性证明了它们的广谱活性;然而，这些聚合物也被发现是溶血性的。
Novel approaches to the development of new antimicrobial compounds and materials remain an important area of research. Many different designs have been reported, including ones incorporating known antibiotics such as ciprofloxacin, 1 N-halamines, 2, 3 and 2, 4 dichlorophenyl4, 5 into polymers. 6, 7 Alternatively, cationic polymers, which have received considerable attention, 8 are well known as disinfectants and include polylysine, 9 quaternary ammonium salts, 10 pyridinium salts, 7, 8 polyguanidines, 11 and polybiguanides. 6, 7, 12 At the same time, host defense peptides represent a large group of natural compounds with broad spectrum antimicrobial activity that also show selectivity between bacterial cells and mammalian red blood cells (RBCs). Examples of host defense peptides include-helical magainin and cecropin, as well as defensins, which contain-strands. They have captured the attention of many researchers, and significant understanding of their essential physiochemical properties and mode of action exists. 13–16 The ability of these peptides to disrupt phospholipid membranes, ultimately killing the cell, is thought to come from the adoption of a facially amphiphilic (FA) structure. 14, 17–19 Thus, the overall structure, rather than the precise chemical composition or amino acid sequence, is of critical importance. This implies that mimicking the FA structure should provide synthetic molecules that have similar biochemical properties, leading to relatively simple polymers that are effective antimicrobial agents and are nontoxic, yet inexpensive and easy to prepare. Amphiphilic helical structures based on synthetic-peptides and peptoids that mimic the overall structure and activity of magainin were recently reported. 20–26 A series of-peptides was synthesized with the same net charge; however, the substitution pattern was varied. 21, 23, 24 It was determined that the most active peptides were those that had the highest degree of facial amphiphilicity. Therefore, it was concluded that the architecture is imperative for antibacterial activity and selectivity, and this was consistent with previous findings from synthetic-peptides. 23, 24 In addition, the widespread observation of FA structures in biology, from peptides to steroids, 27 implies the importance of this architecture. These polyamide examples mimicked both the helical structure and cationic nature of natural host defense peptides. In addition, these mimics are discrete compounds prepared by solid-phase techniques requiring extensive effort and costly purification. The ability to transfer the essential physiochemical properties to simple polymers would provide access to fast, inexpensive molecules for various applications, including medical coatings, antimicrobial tubing, and other materials. The initial work on polymeric systems as nonbiological host defense peptide mimics was conducted with arylamide backbones. 28 These systems were designed to mimic the essential architecture and physiochemical properties of host defense peptides but not the helical structure. Their activity against several bacterial strains demonstrated their broad spectrum activity; however, these polymers were also found to be hemo-