Dipeptides Containing Pyrene and Modified Photochemically Reactive Tyrosine: Noncovalent and Covalent Binding to Polynucleotides

Sviben, Igor; Glavaš, Mladena; Erben, Antonija; Bachelart, Thomas; Pavlović Saftić, Dijana; Piantanida, Ivo; Basarić, Nikola (2023) Dipeptides Containing Pyrene and Modified Photochemically Reactive Tyrosine: Noncovalent and Covalent Binding to Polynucleotides. Molecules, 28 (22). ISSN 1420-3049

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Abstract

Dipeptides 1 and 2 were synthesized from unnatural amino acids containing pyrene as a fluorescent label and polynucleotide binding unit, and modified tyrosine as a photochemically reactive unit. Photophysical properties of the peptides were investigated by steady-state and time-resolved fluorescence. Both peptides are fluorescent (Φf = 0.3–0.4) and do not show a tendency to form pyrene excimers in the concentration range < 10−5 M, which is important for their application in the fluorescent labeling of polynucleotides. Furthermore, both peptides are photochemically reactive and undergo deamination delivering quinone methides (QMs) (ΦR = 0.01–0.02), as indicated from the preparative photomethanolysis study of the corresponding N-Boc protected derivatives 7 and 8. Both peptides form stable complexes with polynucleotides (log Ka > 6) by noncovalent interactions and similar affinities, binding to minor grooves, preferably to the AT reach regions. Peptide 2 with a longer spacer between the fluorophore and the photo-activable unit undergoes a more efficient deamination reaction, based on the comparison with the N-Boc protected derivatives. Upon light excitation of the complex 2·oligoAT10, the photo-generation of QM initiates the alkylation, which results in the fluorescent labeling of the oligonucleotide. This study demonstrated, as a proof of principle, that small molecules can combine dual forms of fluorescent labeling of polynucleotides, whereby initial addition of the dye rapidly forms a reversible high-affinity noncovalent complex with ds-DNA/RNA, which can be, upon irradiation by light, converted to the irreversible (covalent) form. Such a dual labeling ability of a dye could have many applications in biomedicinal sciences.

Item Type:	Article
Uncontrolled Keywords:	dipeptides; noncovalent binding to DNA/RNA; photochemistry; quinone methides; photochemical DNA/RNA alkylation
Subjects:	NATURAL SCIENCES > Chemistry > Analytic Chemistry NATURAL SCIENCES > Chemistry > Organic Chemistry
Divisions:	Division of Organic Chemistry and Biochemistry NMR Center
Projects:	Project title Project leader Project code Project type Fotokemija: Reakcijski mehanizmi i primjene u organskoj sintezi i biologiji-PhotoApp Nikola Basarić; Irena Škorić; Dragana Vuk IP-2019-04-8008 HRZZ Višekromoforne probe za prepoznavanje pojedinih struktura DNA, RNA i proteina-BioMultiChromoProbes Ivo Piantanida IP-2018-01-5475 HRZZ
Depositing User:	Mladena Glavaš
Date Deposited:	17 Dec 2025 08:34
URI:	http://fulir.irb.hr/id/eprint/10535
DOI:	10.3390/molecules28227533

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