Limited treatment options with the use of conventional antibiotics to combat the antibiotic resistance, created a growing need to invent, new potent broad-spectrum antimicrobial drugs. One of the new sources of the prospective alternatives to traditional antibiotics are natural basic antibacterial peptides and their synthetic analogs. Structure-activity studies of this group of compounds showed that they work via membrane-lysis mechanism. Necessary condition for effective interactions of these peptides with slightly negative charged microbial membranes is conformational change allowing separation of positively charged and lypophilic groups (amphiphatic structure). Previously, we attempted to design such structure using appropriate amino acid building blocks and dendrimeric structure. Such de novo approach led to a group of unsymmetrical low molecular weight basic dendrimeric peptides. They showed modest activity against Gram(+) and Gram (-) bacteria [1,2] and variable cytotoxicity strongly correlated with degree of branching. This communication presents synthesis and results of microbiological tests of the two diastereoisomeric groups of dendrimeric peptides (A and B) with C-end modified by aliphatic chains of various length.

The above compounds express high antimicrobial activity, particularly against Gram(+) bacteria including MRSA strains and fungi from C. albicans family. Studies of circular dichroism (CD) showed that these molecules undergo conformational change in presence of micelles that mimic bacterial membranes.

Financial support from Ministry of Education and Informatics of Poland, Grant 3T09B 115 28 is acknowledged.

[1] J. Janiszewska, J. Swieton, A.W. Lipkowski, Z. Urbanczyk-Lipkowska, Bioorg. Med. Chem. Lett. 2003, 13, 3711.
[2] J. Janiszewska, Z. Urbanczyk-Lipkowska, J. Mol. Microbiol. Biotechn. 2007, 13, 220-225.

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