Lind Tania K, Polcyn Piotr, Zielinska Paulina, Cárdenas Marité, Urbanczyk-Lipkowska Zofia
Nano-Science Center and Department of Chemistry, University of Copenhagen, Copenhagen 2100, Denmark.
Institute of Organic Chemistry, Polish Academy of Science, Warsaw 01-224, Poland.
Molecules. 2015 Jan 7;20(1):738-53. doi: 10.3390/molecules20010738.
Antimicrobial drug resistance is a major human health threat. Among the many attempts to tackle this problem, the synthesis of antimicrobial compounds that mimic natural antimicrobial peptides appears as a promising approach. Peptide-based dendrimers can be designed to have higher potency than natural antimicrobial peptides and at the same time they can evade the bacterial defense system. Novel dendrimers with similar chemical structure but varying potency in terms of minimum inhibitory concentration were designed. The dependency between dendrimer structure and antibacterial activity as well as their capacity to attack model cell membranes was studied. The data suggests that supramolecular structure in terms of charge distribution and amphiphilicity, rather than net charge, is the main driver for disruption of cellular membranes and this correlates well with dendrimer hemolytic activity.
抗菌药物耐药性是对人类健康的重大威胁。在解决这一问题的众多尝试中,合成模拟天然抗菌肽的抗菌化合物似乎是一种很有前景的方法。基于肽的树枝状聚合物可以设计成具有比天然抗菌肽更高的效力,同时它们可以规避细菌防御系统。设计了具有相似化学结构但最低抑菌浓度效力不同的新型树枝状聚合物。研究了树枝状聚合物结构与抗菌活性之间的相关性以及它们攻击模型细胞膜的能力。数据表明,就电荷分布和两亲性而言的超分子结构而非净电荷是破坏细胞膜的主要驱动因素,这与树枝状聚合物的溶血活性密切相关。