Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent Attachment

Erben, Antonija; Sviben, Igor; Mihaljević, Branka; Piantanida, Ivo; Basarić, Nikola (2021) Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent Attachment. Molecules, 26 (14). ISSN 1420-3049

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Official URL: https://www.mdpi.com/1420-3049/26/14/4315

Abstract

A series of tripeptides TrpTrpPhe (1), TrpTrpTyr (2), and TrpTrpTyr[CH2N(CH3)2] (3) were synthesized, and their photophysical properties and non-covalent binding to polynucleotides were investigated. Fluorescent Trp residues (quantum yield in aqueous solvent ΦF = 0.03–0.06), allowed for the fluorometric study of non-covalent binding to DNA and RNA. Moreover, high and similar affinities of 2×HCl and 3×HCl to all studied double stranded (ds)-polynucleotides were found (logKa = 6.0–6.8). However, the fluorescence spectral responses were strongly dependent on base pair composition: the GC-containing polynucleotides efficiently quenched Trp emission, at variance to AT- or AU-polynucleotides, which induced bisignate response. Namely, addition of AT(U) polynucleotides at excess over studied peptide induced the quenching (attributed to aggregation in the grooves of polynucleotides), whereas at excess of DNA/RNA over peptide the fluorescence increase of Trp was observed. The thermal denaturation and circular dichroism (CD) experiments supported peptides binding within the grooves of polynucleotides. The photogenerated quinone methide (QM) reacts with nucleophiles giving adducts, as demonstrated by the photomethanolysis (quantum yield ΦR = 0.11–0.13). Furthermore, we have demonstrated photoalkylation of AT oligonucleotides by QM, at variance to previous reports describing the highest reactivity of QMs with the GC reach regions of polynucleotides. Our investigations show a proof of principle that QM precursor can be imbedded into a peptide and used as a photochemical switch to enable alkylation of polynucleotides, enabling further applications in chemistry and biology.

Item Type:

Article

Uncontrolled Keywords:

DNA ; photodeamination ; quinone methide ; RNA ; tripeptide ; tryptophane

Subjects:

NATURAL SCIENCES > Chemistry

Divisions:

Division of Organic Chemistry and Biochemistry

Projects:

Project title	Project leader	Project code	Project type
Fotokemija: Reakcijski mehanizmi i primjene u organskoj sintezi i biologiji	Basarić, Nikola	IP-2019-04-8008	HRZZ
Višekromoforne probe za prepoznavanje pojedinih struktura DNA, RNA i proteina	Piantanida, Ivo	IP-2018-01-5475	HRZZ
Supramolekulska kontrola fotokemijskih reakcija eliminacije	Basarić, Nikola	IP-2014-09-6312	HRZZ