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Basic low molecular dendrimeric peptides designed for better membrane recognition

Jolanta Janiszewska 1Jolanta Solecka 2Aleksandra M. Rajnisz 2Zofia Urbańczyk-Lipkowska 3

1. Industrial Chemistry Research Institute (ICRI), Rydygiera 8, Warszawa 01-793, Poland
2. National Institute of Public Health-National Institute of Hygiene, Warszawa 00-791, Poland
3. Polish Academy of Science, Institute of Organic Chemistry, Kasprzaka 44/52, Warsaw 01-224, Poland


Molecular design and development of anti-infective compounds constitute an important area in modern medicinal research. 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 bacterias’ 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] and variable cytotoxicity strongly correlated with degree of branching [2]. This communication presents synthesis and molecular modeling of three diastereoisomeric groups of dendrimeric peptides with C-end modified by aliphatic chains of various length. Microbiological data for this group of derivatives in comparison with the unmodified compounds will be presented. 3D structure of these molecules, respective distances between positively charged groups (amino groups in form of hydrochloride) and lipophylic elements, obtained from molecular dynamics calculations will be discussed.

1. J. Janiszewska, J. Swieton, A.W. Lipkowski, Z. Urbanczyk-Lipkowska; Bioorg. Med. Chem. Lett. 2003, 13, 3711.

2. B. Klajnert, J. Janiszewska, Z. Urbanczyk-Lipkowska, M. Bryszewska, D. Shcharbin, M. Labieniec; Int. J. Pharm., 2006, 309, 208.


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Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Jolanta Janiszewska
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-16 12:04
Revised:   2010-03-17 09:30