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

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

A series of tripeptides TrpTrpPhe (<b>1</b>), TrpTrpTyr (<b>2</b>), and TrpTrpTyr[CH<sub>2</sub>N(CH<sub>3</sub>)<sub>2</sub>] (<b>3</b>) were synthesized, and their photophysical properties and non-covalent binding to polynucle...

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Main Authors: Antonija Erben, Igor Sviben, Branka Mihaljević, Ivo Piantanida, Nikola Basarić
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Molecules
Subjects:
DNA
photodeamination
quinone methide
RNA
tripeptide
tryptophane
Online Access:https://www.mdpi.com/1420-3049/26/14/4315
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spelling doaj-4153932ca1f54ee4be41611e90dd98592021-07-23T13:56:47ZengMDPI AGMolecules1420-30492021-07-01264315431510.3390/molecules26144315Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent AttachmentAntonija Erben0Igor Sviben1Branka Mihaljević2Ivo Piantanida3Nikola Basarić4Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10 000 Zagreb, CroatiaDepartment of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10 000 Zagreb, CroatiaDepartment of Material Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10 000 Zagreb, CroatiaDepartment of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10 000 Zagreb, CroatiaDepartment of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10 000 Zagreb, CroatiaA series of tripeptides TrpTrpPhe (<b>1</b>), TrpTrpTyr (<b>2</b>), and TrpTrpTyr[CH<sub>2</sub>N(CH<sub>3</sub>)<sub>2</sub>] (<b>3</b>) were synthesized, and their photophysical properties and non-covalent binding to polynucleotides were investigated. Fluorescent Trp residues (quantum yield in aqueous solvent Φ<sub>F</sub> = 0.03–0.06), allowed for the fluorometric study of non-covalent binding to DNA and RNA. Moreover, high and similar affinities of <b>2×HCl</b> and <b>3×HCl</b> to all studied double stranded (ds)-polynucleotides were found (log<i>K</i><sub>a</sub> = 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 Φ<sub>R</sub> = 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.https://www.mdpi.com/1420-3049/26/14/4315DNAphotodeaminationquinone methideRNAtripeptidetryptophane
collection DOAJ
language English
format Article
sources DOAJ
author Antonija Erben
Igor Sviben
Branka Mihaljević
Ivo Piantanida
Nikola Basarić
spellingShingle Antonija Erben
Igor Sviben
Branka Mihaljević
Ivo Piantanida
Nikola Basarić
Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent Attachment
Molecules
DNA
photodeamination
quinone methide
RNA
tripeptide
tryptophane
author_facet Antonija Erben
Igor Sviben
Branka Mihaljević
Ivo Piantanida
Nikola Basarić
author_sort Antonija Erben
title Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent Attachment
title_short Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent Attachment
title_full Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent Attachment
title_fullStr Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent Attachment
title_full_unstemmed Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent Attachment
title_sort non-covalent binding of tripeptides-containing tryptophan to polynucleotides and photochemical deamination of modified tyrosine to quinone methide leading to covalent attachment
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2021-07-01
description A series of tripeptides TrpTrpPhe (<b>1</b>), TrpTrpTyr (<b>2</b>), and TrpTrpTyr[CH<sub>2</sub>N(CH<sub>3</sub>)<sub>2</sub>] (<b>3</b>) were synthesized, and their photophysical properties and non-covalent binding to polynucleotides were investigated. Fluorescent Trp residues (quantum yield in aqueous solvent Φ<sub>F</sub> = 0.03–0.06), allowed for the fluorometric study of non-covalent binding to DNA and RNA. Moreover, high and similar affinities of <b>2×HCl</b> and <b>3×HCl</b> to all studied double stranded (ds)-polynucleotides were found (log<i>K</i><sub>a</sub> = 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 Φ<sub>R</sub> = 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.
topic DNA
photodeamination
quinone methide
RNA
tripeptide
tryptophane
url https://www.mdpi.com/1420-3049/26/14/4315
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