Klajnert B, Janiszewska J, Urbanczyk-Lipkowska Z, Bryszewska M, Shcharbin D, Labieniec M
Department of General Biophysics, University of Lodz, 90-237 Lodz, Poland.
Int J Pharm. 2006 Feb 17;309(1-2):208-17. doi: 10.1016/j.ijpharm.2005.10.039. Epub 2006 Jan 18.
A series of new, low molecular mass, lysine-based peptide dendrimers with varying distribution of cationic and aromatic groups in the structure were synthesized. They expressed antimicrobial activity against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria as well as against fungal pathogens (Candida albicans). Their cytotoxic, haematotoxic, and genotoxic effects were studied. It appears that degree of branching and steric distribution and types of hydrophobic (aromatic) groups and cationic centres are important components of dendrimeric structure and influence both antimicrobial potency and toxicity. Such 3D structure of our dendrimers mimics that of the natural antimicrobial peptides and can be achieved by application of dendrimer chemistry.
合成了一系列新型的、低分子量的、基于赖氨酸的肽树枝状大分子,其结构中阳离子和芳香族基团的分布各不相同。它们对革兰氏阳性菌(金黄色葡萄球菌)、革兰氏阴性菌(大肠杆菌)以及真菌病原体(白色念珠菌)均表现出抗菌活性。研究了它们的细胞毒性、血液毒性和遗传毒性。结果表明,树枝状大分子结构的分支度、空间分布、疏水(芳香)基团类型和阳离子中心是影响抗菌效力和毒性的重要组成部分。我们的树枝状大分子的这种三维结构模仿了天然抗菌肽的结构,可通过应用树枝状大分子化学来实现。