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Nucleic Acids Research Dec 1987Evidence is summarized showing that thymine methyls are as important in the recognition of specific sequences by proteins as are the more widely recognized hydrogen... (Review)
Review
Evidence is summarized showing that thymine methyls are as important in the recognition of specific sequences by proteins as are the more widely recognized hydrogen bonding sites of bases in the major groove (1). Strongest evidence has come from experiments using functional group mutagenesis (2) in which thymines in a specific recognition sequence (e.g., promoters, operators and restriction sites) are replaced by oligonucleotide synthesis with methyl-free uracil or cytosine and 5-methylcytosine. Such experiments have shown that thymine methyls can provide contact points via van der Waals interactions with amino acid side chains of specific DNA binding proteins. Actual contact between a thymine methyl and carbons of a glutamine side chain has been observed in a cocrystal of the phage 434 repressor and its operator by X-ray analysis. The issue of why thymine occurs in DNA is discussed in light of these findings.
Topics: Bacterial Proteins; Base Sequence; DNA (Cytosine-5-)-Methyltransferases; DNA, Bacterial; DNA-Binding Proteins; Methylation; Thymine
PubMed: 3320959
DOI: 10.1093/nar/15.23.9975 -
Molecules (Basel, Switzerland) Jun 2020A series of TMPK (TMPK) inhibitors based on a reported compound were synthesized and evaluated for their capacity to inhibit TMPK catalytic activity and the growth of...
A series of TMPK (TMPK) inhibitors based on a reported compound were synthesized and evaluated for their capacity to inhibit TMPK catalytic activity and the growth of a virulent strain (H37Rv). Modifications of the scaffold of failed to afford substantial improvements in TMPK inhibitory activity and antimycobacterial activity. Optimization of the substitution pattern of the D ring of resulted in compound with improved TMPK inhibitory potency (three-fold) and H37Rv growth inhibitory activity (two-fold). Moving the 3-chloro substituent of to the -position afforded isomer , which, despite a 10-fold increase in IC-value, displayed promising whole cell activity (minimum inhibitory concentration (MIC) = 12.5 μM).
Topics: Antitubercular Agents; Bacterial Proteins; Enzyme Inhibitors; Humans; Models, Molecular; Molecular Structure; Mycobacterium tuberculosis; Nucleoside-Phosphate Kinase; Structure-Activity Relationship; Thymine
PubMed: 32560578
DOI: 10.3390/molecules25122805 -
Proceedings of the National Academy of... Feb 1977DNA can be sequenced by a chemical procedure that breaks a terminally labeled DNA molecule partially at each repetition of a base. The lengths of the labeled fragments...
DNA can be sequenced by a chemical procedure that breaks a terminally labeled DNA molecule partially at each repetition of a base. The lengths of the labeled fragments then identify the positions of that base. We describe reactions that cleave DNA preferentially at guanines, at adenines, at cytosines and thymines equally, and at cytosines alone. When the products of these four reactions are resolved by size, by electrophoresis on a polyacrylamide gel, the DNA sequence can be read from the pattern of radioactive bands. The technique will permit sequencing of at least 100 bases from the point of labeling.
Topics: Adenine; Base Sequence; Biochemical Phenomena; Biochemistry; Cytosine; DNA; DNA Restriction Enzymes; Guanine; Hydrazines; Methods; Nucleic Acid Hybridization; Thymine
PubMed: 265521
DOI: 10.1073/pnas.74.2.560 -
Physical Chemistry Chemical Physics :... Jul 2006We discuss the photochemistry and photodissociation dynamics of thymine as revealed by two-colour photofragment Doppler spectroscopy and by one-colour slice imaging....
We discuss the photochemistry and photodissociation dynamics of thymine as revealed by two-colour photofragment Doppler spectroscopy and by one-colour slice imaging. Thymine is optically excited into the pipi* state, known to deactivate quickly. The H atom photofragment spectra are dominated by two-photon excitation processes with subsequent statistical dissociation. This can be explained by absorption of a second photon from a long-lived dark state to a highly excited state that quickly deactivates to the electronic ground state. No evidence was found for an important role of the pisigma* excited state identified in adenine and many other heterocyclic molecules.
Topics: Algorithms; Computer Simulation; Light; Models, Chemical; Models, Molecular; Molecular Conformation; Photochemistry; Quantum Theory; Thymine
PubMed: 16880915
DOI: 10.1039/b518443f -
Molecules (Basel, Switzerland) Jun 2022A DNA Holliday junction (HJ) has been used as a versatile scaffold to create a variety of covalently templated molecular dye aggregates exhibiting strong excitonic...
A DNA Holliday junction (HJ) has been used as a versatile scaffold to create a variety of covalently templated molecular dye aggregates exhibiting strong excitonic coupling. In these dye-DNA constructs, one way to attach dyes to DNA is to tether them via single long linkers to thymine modifiers incorporated in the core of the HJ. Here, using photoinduced [2 + 2] cycloaddition (photocrosslinking) between thymines, we investigated the relative positions of squaraine-labeled thymine modifiers in the core of the HJ, and whether the proximity of thymine modifiers correlated with the excitonic coupling strength in squaraine dimers. Photocrosslinking between squaraine-labeled thymine modifiers was carried out in two distinct types of configurations: adjacent dimer and transverse dimer. The outcomes of the reactions in terms of relative photocrosslinking yields were evaluated by denaturing polyacrylamide electrophoresis. We found that for photocrosslinking to occur at a high yield, a synergetic combination of three parameters was necessary: adjacent dimer configuration, strong attractive dye-dye interactions that led to excitonic coupling, and an A-T neighboring base pair. The insight into the proximity of dye-labeled thymines in adjacent and transverse configurations correlated with the strength of excitonic coupling in the corresponding dimers. To demonstrate a utility of photocrosslinking, we created a squaraine tetramer templated by a doubly crosslinked HJ with increased thermal stability. These findings provide guidance for the design of HJ-templated dye aggregates exhibiting strong excitonic coupling for exciton-based applications such as organic optoelectronics and quantum computing.
Topics: Coloring Agents; Cross-Linking Reagents; DNA, Cruciform; Electrophoresis, Gel, Two-Dimensional; Photochemistry; Thymine
PubMed: 35807250
DOI: 10.3390/molecules27134006 -
Journal of Molecular Biology Feb 1962
Topics: Photochemistry; Pyrimidine Dimers; Thymine
PubMed: 14451976
DOI: 10.1016/s0022-2836(62)80042-4 -
Photochemistry and Photobiology May 2022Among the naturally occurring nucleobases, thymine presents the lowest triplet state, hence it represents a hotspot for energy transfer and photosensitization. In turn,...
Among the naturally occurring nucleobases, thymine presents the lowest triplet state, hence it represents a hotspot for energy transfer and photosensitization. In turn, the population of the triplet state may lead to thymine dimerization and hence to the production of toxic DNA lesions and has been the subject of intensive theoretical and experimental investigations. Relying on QM/MM molecular dynamics simulations, we have sought to situate the energy of the lowest triplet state of thymine embedded in a B-DNA environment. The energy gap varies between 305 and 329 kJ mol when a single thymine is treated at the quantum chemistry level, depending on its position in the model double-stranded 16-bp oligonucleotide. The energy of triplet state decreases up to 300 kJ mol , due to polarization effects, when we consider coupled stacked nucleobases up to the inclusion of four nucleobases. Our value lies in good agreement with the energy inferred experimentally by Miranda and coworkers (270 kJ mol ), and our theoretical exploration opens the door to investigations toward other more complex and biologically relevant environments, such as thymines embedded in nucleosome core particles. Our investigations also provide a reference for further studies using semi-empirical approaches such as density functional-based tight-binding, allowing to further rationalize sequence effects.
Topics: DNA; DNA, B-Form; Dimerization; Molecular Dynamics Simulation; Thymine
PubMed: 34699615
DOI: 10.1111/php.13549 -
The Journal of Physical Chemistry. B Feb 2019Ionizing radiation can excite the cellular medium to produce secondary electrons that can subsequently cause damage to DNA. The damage is believed to occur via...
Ionizing radiation can excite the cellular medium to produce secondary electrons that can subsequently cause damage to DNA. The damage is believed to occur via dissociative electron attachment (DEA). In DEA, the electron is captured by a molecule in a resonant antibonding state and a transient negative ion is formed. If this ion survives against electron autodetachment, then bonds within the molecule may dissociate as energy is transferred from the electronic degrees of freedom into vibrational modes of the molecule. We present a model for studying the effect that transferring kinetic energy into the vibrational modes of a molecule in this way has on a DNA nucleobase. We show that when the base is in an aqueous environment, dissociation is affected by interactions with the surrounding water molecules. In particular, hydrogen bonding between the nucleobase and the solvent can suppress the dissociative channel.
Topics: Density Functional Theory; Electrons; Hydrogen Bonding; Solvents; Thymine
PubMed: 30694675
DOI: 10.1021/acs.jpcb.8b11621 -
The Journal of Organic Chemistry Aug 2013A template tetra-coupled with thymidylic acid through a phosphate linkage was characterized in methanol for emergent properties of nucleobase tetrad formation....
A template tetra-coupled with thymidylic acid through a phosphate linkage was characterized in methanol for emergent properties of nucleobase tetrad formation. Intramolecular hydrogen bonded base pairing in the absence of a cation was indicated for the thymidylic acid species supporting a monomeric template-assembled structure. Thus, an initial report of a stabilized individual thymine tetrad assembly is presented here. Consistent with previous investigations, a deoxyguanylic acid variant templated an analogous methanolic monomeric G-tetrad in comparison to the thymine species.
Topics: Hydrogen Bonding; Molecular Structure; Thymidine Monophosphate; Thymine
PubMed: 23875642
DOI: 10.1021/jo401281p -
Chemistry (Weinheim An Der Bergstrasse,... Nov 2015A new mechanism of photosensitized formation of thymine (Thy) dimers is proposed, which involves generation of a delocalized triplet excited state as the key step. This...
A new mechanism of photosensitized formation of thymine (Thy) dimers is proposed, which involves generation of a delocalized triplet excited state as the key step. This is supported by chemical evidence obtained by combining one benzophenone and two Thy units with different degrees of freedom, whereby the photoreactivity is switched from a clean Paternò-Büchi reaction to a fully chemo-, regio-, and stereoselective [2+2] cycloaddition.
Topics: Cycloaddition Reaction; Dimerization; Energy Transfer; Photochemistry; Photosensitizing Agents; Pyrimidine Dimers; Stereoisomerism; Thymine
PubMed: 26462463
DOI: 10.1002/chem.201502719