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Design of novel peptide dendrimers: antimicrobial and anticancer activity

Zofia Lipkowska 1Piotr Polcyn 1Paulina Zielińska 1Aleksandra M. Rajnisz 2Jolanta Solecka 2

1. Polish Academy of Science, Institute of Organic Chemistry, Kasprzaka 44/52, Warsaw 01-224, Poland
2. National Institute of Public Health-National Institute of Hygiene (NIZP-PZH), Chocimska, Warszawa 00-791, Poland


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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Presentation: Oral at VII Multidyscyplinarna Konferencja Nauki o Leku, by Zofia Lipkowska
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-16 08:25
Revised:   2010-03-17 10:20