Fluorescent Analogues of FRH Peptide: Cu(II) Binding and Interactions with ds-DNA/RNA

Košćak, Marta; Krošl, Ivona; Žinić, Biserka; Piantanida, Ivo (2022) Fluorescent Analogues of FRH Peptide: Cu(II) Binding and Interactions with ds-DNA/RNA. Chemosensors, 10 (1). ISSN 2227-9040

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Official URL: https://www.mdpi.com/2227-9040/10/1/34/htm

Abstract

Four novel peptidoids, derived from the 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. So the constructed Phe-Lys- Ala(triazole) (FKA(triazole)) peptidoids bind Cu2+ cations in water with a strong, nanomolar affinity comparable to the parent FRH and its known analogues, demonstrating that triazole can coordinate copper similarly as histidine. Moreover, even short KA(triazole)coumarin showed submicromolar affinity to Cu2+. Only FKA(triazole)coumarin with free amino groups and its shorter analog KA(triazole)coumarin showed strong induced 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 ds-DNA and ds-RNA, binding within DNA/RNA grooves. Intriguingly, only peptidoid com-plexes with Cu2+ strongly stabilize ds-DNA and ds-RNA against thermal denaturation, suggesting significant interactions of Cu2+ cation within the DNA/RNA binding site.

Item Type:

Article

Uncontrolled Keywords:

fluorescent peptide ; circular dichroism ; copper-binding ; DNA/RNA binding

Subjects:

NATURAL SCIENCES > Chemistry

Divisions:

Division of Organic Chemistry and Biochemistry

Projects: