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Non-Covalent Binding of Tripeptides-Containing Tryptophan to Polynucleotides and Photochemical Deamination of Modified Tyrosine to Quinone Methide Leading to Covalent Attachment
- Source :
- Molecules, Volume 26, Issue 14, Molecules, Vol 26, Iss 4315, p 4315 (2021)
- Publication Year :
- 2021
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2021.
-
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.
- Subjects :
- Circular dichroism
Base pair
tripeptide
Pharmaceutical Science
Organic chemistry
Peptide
Tripeptide
010402 general chemistry
Photochemistry
01 natural sciences
Article
Analytical Chemistry
chemistry.chemical_compound
QD241-441
photodeamination
Drug Discovery
tryptophane
quinone methide
Indolequinones
Physical and Theoretical Chemistry
chemistry.chemical_classification
010405 organic chemistry
Oligonucleotide
Tryptophan
DNA
RNA
Photochemical Processes
Quinone methide
0104 chemical sciences
Chemistry
chemistry
Deamination
Chemistry (miscellaneous)
Covalent bond
Polynucleotide
Poly A-U
Molecular Medicine
Oligopeptides
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....5c8768794f831583fb00254b670b7302
- Full Text :
- https://doi.org/10.3390/molecules26144315