Luliberin Analogues Exhibiting a Cytotoxic Effect on Tumor Cells In Vitro

S. V. Burova,# T. V. Yablokovaa, M. Yu. Dorosha, Z. P. Shkarubskayaa, M. Blankb, N. Epsteinb, and M. Fridkinc

# Phone/fax: (812) 323-3607; e-mail:
a Institute of Macromolecular Compounds, Russian Academy of Sciences, Bol'shoi pr. 31, St. Petersburg, 119004 Russia
b Chaim Sheba Medical Center, Tel-Hashomer, Israel
c Weizmann Institute of Science, Rehovot, Israel
Received October 26, 2005; in final form, November 14, 2005

Abstract: Luliberin analogues modified at the N-terminus were synthesized to search for drugs exerting a cytotoxic effect on cells of hormone-dependent tumors. A synthetic scheme effective in the preparation of analogues containing fatty acid residues was proposed. The cytotoxic effect of the peptides was studied on a number of cell lines of human tumors in vitro. The dependence of the antitumor effect on the length of peptide chain, amino acid sequence, and structure of the N-terminal group was demonstrated. Modification with palmitic acid was found to result in highly active compounds in the case of analogues containing more than ten aa, whereas modifications with lauric, caproic, or trimethylacetic acid led to compounds with significantly lower activities. Analogues of luliberin containing a palmitic acid residue and effectively inhibiting the growth of tumor cells in vitro were synthesized.

Key words: antitumor activity, luliberin, palmitic acid, synthetic peptides

Russian Journal of Bioorganic Chemistry 2006, 32 (5):413-419