Dendrimers are macromolecular compounds of branched structure, most widely investigated as prospective drug carriers. Here we present design and biological activity of a novel type of peptide dendrimers based on highly branched tetra-arm core (A) with intrinsic antimicrobial properties. They are branched analogs of natural antimicrobial peptides and therefore, are characterized by amphiphilic structure and positive charge.

The tetra-branched dendrimeric peptides described here demonstrate higher activity against Gram(+) and Gram(-) strains, including MRSA and ESBL reference strains, than similarly substituted respective dendrimers built around (Lys)₂Lys scaffolds [1]. More hydrophobic molecules are active against human melanoma cancer cells. Both antimicrobial potency  and  hemolytic  properties strongly depend on molecular structure and character of the R² groups. Electron microscopy and DSC studies on interactions with model multilamelar vesicles confirm their activity on phospholipid bilayers [2].

 Fig. 1. General structure of dendrimers

These compounds are fully characterized by NMR spectroscopy. The secondary structure of dendrimers was estimated by CD spectroscopy in water, TFE and anisotropic environment of SDS micelles. The designed compounds overcome several disadvantages of the natural antimicrobial peptides including high cost of preparation and low plasma half-life.

 Authors acknowledge financial support from the Ministry of Science and High Education, grant N204 239436 and EC project Normolife.

 [1] J. Janiszewska, Z. Urbańczyk-Lipkowska: Amphiphilic dendrimeric peptides as model non-sequential pharmacophores with antimicrobial properties. J Mol Microbiol Biotechnol 2007, 13, 220-225

[2] Klajnert, B.; Janiszewska, J.; Urbanczyk-Lipkowska, Z.; Bryszewska, A.; Epand, R.M. DSC studies on interactions between low molecular mass peptide dendrimers and model lipid membranes. Int. J. Pharm. 2006, 327, 145-152.

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