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Genetics
Published in Rachel U Sidwell, Mike A Thomson, Concise Paediatrics, 2020
Rachel U Sidwell, Mike A Thomson
This occurs in a sequence: DNA helix splits to form two single strandsNew complementary base pairs, i.e. C with G, and T with A, are added to the single strands at the 3′ end (so the new DNA replication grows from 5′ to 3’). DNA polymerase enzyme adds the new nucleotides.
Nucleic Acids
Published in Danilo D. Lasic, LIPOSOMES in GENE DELIVERY, 2019
A very important area in medicinal chemistry is the interaction of DNA with drugs. Four major groups of drugs as determined by their interactions with DNA can be identified: (1) alkylating agents (mitomycin C, cisplatin), (2) DNA strand-breaking compounds (bleomycin), (3) intercalating agents (doxorubicin, actinomycin D), and (4) drugs that modify DNA in the minor groove. The detailed mechanism of these interactions is still not understood. For instance, the intercalation mechanism of doxorubicin was confirmed by X-ray structure analysis, but was on the other hand never fully supported by structure–activity relationships. Differences were explained by other effects such as the effect on cell membrane and the oxidative DNA damage mechanism. It is also likely that localization in the DNA helix becomes important only at certain steps, such as in topological processing of DNA (Hurley, 1989).
Topoisomerase II Inhibition by Antitumor Intercalators and Demethylepipodophyllotoxins
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
Chromatin organization has been described in recent reviews.10,11 The double-stranded DNA helix is wrapped around nucleosomes (approximately 150 bp and 1.5 superhelical turns). Linker regions between nucleosomes (50 to 100 bp) are bound to H1 histone. Nucleosome-DNA complexes form solenoid structures (30-nm diameter fibers) which are organized into chromatin loops (Figure 2). Loop size varies between 20 ~ 100 kbp and is determined by the attachment of the extremities of the loop to the chromosome scaffold (nuclear matrix attachment points). There is good evidence that topo II is bound at these attachment sites, since topo II has been identified as the previously described scaffolding protein, SC1.12 Both SC1 and topo II have similar molecular weights (170 kDa) and im-munoreactivities. In addition, SC1 antibodies block topo II function.13
Insights and controversies on sunscreen safety
Published in Critical Reviews in Toxicology, 2020
Juliana P. Paiva, Raiane R. Diniz, Alvaro C. Leitão, Lucio M. Cabral, Rodrigo S. Fortunato, Bianca A. M. C. Santos, Marcelo de Pádula
The most frequent DNA lesions generated directly by UV radiation are the pyrimidine cyclobutane dimmers (CPDs) and the 6-4-pyrimidine-pyrimidone photoproducts (6-4PPs). These lesions are responsible for promoting structural alterations to the DNA helix, which can lead to the inhibition of replication and transcription. CPDs are formed after a covalent bond between two adjacent pyrimidine bases generating a cyclobutane ring formed from the saturation of the double bond between carbons 5 and 6 of the neighbor pyrimidine nitrogen bases (Friedberg et al. 2006). These bonds have a high mutagenic potential and need to be corrected by DNA repair mechanisms (Mancebo et al. 2014). The 6-4PPs are characterized by a covalent bond between the 5′ end of carbon 6 from a base to the 3′ end of carbon 4 from its adjacent base (Friedberg et al. 2006). These two lesions appear to induce differential biological effects in the cell exposed to UV. Scientific evidence suggests that 6-4PPs participate more effectively in UV-induced apoptosis, whereas CPDs appear to be more important in arresting progression cell cycle (Lo et al. 2005). The conversion of 6-4PPs into their Dewar valence isomers, other type of lesion, results from the intramolecular electrocyclization of the pyrimidone ring after the photon absorption (Perdiz et al. 2000; Douki 2016). The formation of a Dewar isomer requires at least two photons: the first induces the 6-4PP and the second, arisen from UVA, is required for the isomerization of the initial 6-4PP.
DNA binding, BSA interaction and in-vitro antimicrobial studies of Cu(II), Co(III), Ni(II) and VO(IV) complexes with a new Schiff base
Published in Egyptian Journal of Basic and Applied Sciences, 2020
Disha Sharma, Hosakere D. Revanasiddappa, Basavegowda Jayalakshmi
The interaction between the metal complexes and DNA was further confirmed by viscometric measurements. Although spectroscopic methods provide important evidence to support the mode of binding of metal complexes to DNA, hydrodynamic measurements are considered to be the best binding interaction of DNA in solution, without a crystallographic data [31,32]. Upon interaction of metal complex with DNA, this results in lengthening of its helix and can also accommodate ligand with increasing in viscosity. If partial binding of ligand leads to kink or bend of DNA helix with decrease in DNA length along with decrease in viscosity, a remarkable increase in DNA viscosity indicates intercalation mode of interaction of complex with DNA. This change has been observed in Figure 13. The results obtained from spectroscopic studies are in agreement with this result.
Design, synthesis, molecular modelling, and biological evaluation of novel substituted pyrimidine derivatives as potential anticancer agents for hepatocellular carcinoma
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Naglaa Mohamed Ahmed, Mahmoud Youns, Moustafa Khames Soltan, Ahmed Mohammed Said
One possible reason for the potent anticancer activity of the designed compounds is the presence of the planar aromatic tricyclic (Anthracene) ring. The anthracene containing compounds, such as DOX or the designed compounds 4a-t, are hypothesised to function primarily at the DNA level by blocking the replication and transcription processes. The binding to DNA structure is generally hypothesised to be essential for the cytotoxic activity of these compounds. To predict and understand the possible binding mode and the respective interactions of the designed compounds with the cell DNA structure, the co-crystal structure of DOX-DNA sequence d(CGATCG) complex (PDB: 1D12) was used49. As shown in Figure 10, the anthracene planar chromophore of compound 4e is intercalated with the DNA helix. While the rest of the structure is directed towards the minor groove of DNA forming additional van der Waals interactions.