title: Reversible Hydrolysis Reaction with the Spore Photoproduct under Alkaline Conditions.
abstract: DNA lesions may reduce the electron density at the nucleobases, making them prone to further modifications upon the alkaline treatment. The dominant DNA photolesion found in UV-irradiated bacterial endospores is a thymine dimer, 5-thyminyl-5,6-dihydrothymine, i.e., the spore photoproduct (SP). Here we report a stepwise addition/elimination reaction in the SP hydrolysis product under strong basic conditions where a ureido group is added to the carboxyl moiety to form a cyclic amide, regenerating SP after eliminating a hydroxide ion. Direct amidation of carboxylic acids by reaction with amines in the presence of a catalyst is well documented; however, it is very rare for an amidation reaction to occur without activation. This uncatalyzed SP reverse reaction in aqueous solution is even more surprising because the carboxyl moiety is not a good electrophile due to the negative charge it carries. Examination of the base-catalyzed hydrolyses of two other saturated pyrimidine lesions, 5,6-dihydro-2'-deoxyuridine and pyrimidine (6-4) pyrimidone photoproduct, reveals that neither reaction is reversible even though all three hydrolysis reactions may share the same gem-diol intermediate. Therefore, the SP structure where the two thymine residues maintain a stacked conformation likely provides the needed framework enabling this highly unusual carboxyl addition/elimination reaction.
authors.affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis (IUPUI) , 402 North Blackford Street, Indianapolis, Indiana, 46202, United States.
authors.forename: Surya
authors.initials: S
authors.lastname: Adhikari
authors.affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis (IUPUI) , 402 North Blackford Street, Indianapolis, Indiana, 46202, United States.
authors.forename: Gengjie
authors.initials: G
authors.lastname: Lin
authors.affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis (IUPUI) , 402 North Blackford Street, Indianapolis, Indiana, 46202, United States.|Department of Biochemistry and Molecular Biology & Department of Dermatology, Indiana University School of Medicine , Indianapolis, Indiana 46202, United States.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D000468:Alkalies / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013171:Spores, Bacterial
chemical_list: D000468:Alkalies