engleski

Fluorescent analogues of FRH peptide: Cu(II) binding and interactions with ds-DNA/RNA

The biological function of many proteins is based on creating metal complexes, in which metals have structural and functional roles. Peptide bonds, metal-coordinating centers in amino acid (AA) side chains (e.g. imidazole group of histidine), and the aromatic rings in AA can efficiently interact with metals. Therefore, four novel peptidoids, derived from naturally occurring Phe-Arg-His (FRH) peptide motif, were prepared by replacing the histidine heterocycle with triazole and consequent triazole-fluorophore (coumarin) extension and also replacing arginine with less voluminous lysine. The constructed Phe-Lys-Ala(triazole) (FKA(triazole)) peptoids bind Cu2+ cations in water with strong, nanomolar affinity, comparable to the parent FRH, demonstrating that triazole can coordinate Cu2+ similarly as histidine. Even short KA(triazole)coumarine showed submicromolar affinity to Cu2+. Only FKA(triazole)coumarin with free amino groups and its shorter analogue KA(triazole)coumarin showed strong induced circular dichroism (CD) spectra upon Cu2+ cation binding. Thus, KA(triazole)coumarin can be considered as the shortest peptidoid sequence with highly sensitive fluorescent and chiral CD response for Cu2+ cation, encouraging further studies with other metal cations. The FKA(triazole)coumarin peptidoids show biorelevant, 10 μM affinity to double-stranded (ds)-DNA and ds- RNA, binding within DNA/RNA grooves.

coumarine ; FRH peptides ; binding of Cu2+ ; nonconvalent interactions with DNA/RNA ; circular dichroism

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