engleski

HYDRAZINO PEPTIDOMIMETICS FOR NUCLEIC ACIDS BINDING

Peptidomimetics are compounds able to mimic structure and function of natural peptides or proteins, and also circumvent some of the problems associated with their natural counterparts, like poor stability and bioavailability. By mimicking protein secondary structures, peptidmimtics may interfere with enzyme-substrate, protein-protein or protein- nucleic acid interactions. Thus, they are important tools in drug design. Hydrazino derivatives of natural amino acids are building blocks designed by Cβ-N replacement in β-peptides. The hydrazine fragment induces hydrazino turn conformation where additional nitrogen acts both as H-bond donor and acceptor. It is assumed that hydrazino moiety incorporated into peptide sequence would direct peptide backbone to cylinder-like shape convenient for DNA minor/RNA major groove and could increase number of possible hydrogen bonds within DNA/RNA grooves. Presence of positively charged lysine is expected to contribute to the DNA/RNA binding through electrostatic interactions, while fluorescent dye (AlaP) would contribute to binding and reporting the recognition by phenanthridine excimer fluorescence. Peptides were prepared comprising solution-phase methodology.Interaction of novel peptides with ss- and ds- DNA/RNA were analyzed using spectroscopic methods. All peptides containing phenanthridine amino acid (AlaP) revealed binding to ds-polynucleotides, probably as groove binders. Binding affinities and the intensity of spectroscopic response (CD, fluorescence) were decreased for each additional hydrazino group. Interestingly, peptides influenced stronger on CD spectra of ss-polynucleotide. Peptide H-Lys-hLeu-Leu-Gly- AlaP-OH caused remarkable increase of poly G CD bands, pointing strong influence on secondary structure of ss-polynucleotide.

peptidomimetics; hydrazino acids; DNA/RNA binding

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