[7][“Molecule S”

Formation of the minor products is initiated by hydration of the thymine radical cation double bond.These primary oxidation products are formed, in part, by a tandem process in which a peroxyl radical reacts with an adjacent thymine resulting in damage to both bases in the TT step.The relative yield of products is determined by the difference in free energies of the Targetmol’s Voriconazole transition states leading to their formation.In DNA that contains guanines, the energy of the transition state for its reaction with HO is lower than that for the reaction of any other base radical cation.For DNA that contains only AT base pairs, the activation free energy for reaction at the thymine radical cation is lower than that for reaction at the adenine radical cation.Molecular relaxation, primarily of solvating HO molecules, in the vicinity of the hole trap it as a polaron that hops from one site to another in a process that is gated, in part, by thermal motions of cationic counterions and their associated hydration environment.Reactions of the radical cations result in damaged nucleobases.The particular site for reaction is determined by kinetic or thermodynamic control, governed by the sequence of nucleobases.The proclivity for reaction at a specic G is determined by both electronic and steric factors and is facilitated by proton transfer to a neighboring phosphate group.If there is no suitable guanine, reaction occurs at TT steps largely by a tandem reaction process that damages both bases.Science. Nature. Science. Meaningful slopes are obtained only from experiments carried to low conversion where each DNA molecule reacts once or not at all; that is, singlehit conditions.A model for the situation in DNA.This work was carried out in collaboration with Professor Jean Cadet and Dr.Vol, No. February ACCOUNTS OF CHEMICAL RESEARCH Structural modifications to DNA mainly arise from modifications in its bases that primarily occur due to their exposure to different reactive species.These structural modifications are involved in mutation, cancer and many other diseases.As it has the least oxidation potential among all the DNA bases, guanine is frequently attacked by reactive species, producing a plethora of lethal lesions.Fortunately, living cells are evolved with intelligent enzymes that continuously protect DNA from such damages.This review provides an overview of different guanine lesions formed due to reactions of guanine with different reactive species.Dismutation of O by superox idedismutaseproducesH O. Apart from this, different enzymes such as several oxidases can also produce HO in cells.OH radicals are very reactive and can perturb structures of all components of the DNA.Formation of nitric oxide, which is very reactive.More interestingly, ONOO itself is capable of generating other reactive species that are very reactive.In addition to normal metabolic activities, ionizing radiation and surgical resection at any part of the body may help in generation of reactive species. Other than reactive species, chemicals such as different alkylating and nitrating agents and highenergy radiation are also capable of damaging DNA.Among all the DNA bases, guanine has the least oxidation potential, because of which it is frequently attacked by different reactive species.Different guanine lesions formed in this way can induce mutagenesis, crosslinks between DNA strands and proteins, thereby affecting DNA replication and transcription.

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