engleski

Conformational Analysis and Biological Evaluation of Ferrocene Peptidomimetics

The low metabolic stability as well as poor absorption and undesired side effects caused by interaction of conformationally changeable peptides with diverse receptors represent the major obstacles to their pharmaceutical application. The development of peptidomimetics with rigidified conformation and improved biostability has proven as an efficient step towards overcoming these drawbacks. One of the strategic approaches to the peptidomimetic design is based on the utilization of small molecular scaffold capable of inducing the secondary structure upon incorporation into peptide backbone. In this respect, 1, 1′-disubstituted ferrocene (Fc) scaffolds, equipped with hydrogen bonding functionalities, have been employed to nucleate turns and -sheet-like structures.1 The previous results2 obtained on peptides I composed of ‒NH‒Fc‒CO‒ scaffold and Pro confirmed the presence of γ-turn, realized through intrachain hydrogen bonding. Their biological evaluation, performed with regard to antiproliferative effect on MCF7 and HeLa cell line, has been demonstrated no or rather modest cytotoxic effect. In order to improve the biological activity of the ferrocene conjugates with Pro I, we have synthesized their higher homologues II with inserted Ala unit between ferrocene unit and Pro. This structural modification was found to influence the conformational pattern of the peptides II, but the enhanced cytotoxicity was not observed.

ferrocene, peptidomimetic, conformational analysis, biological activit

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