A Kinetic Study of the Ultraviolet Decomposition of Biochemical Derivatives of Nucleic Acid. I. Purines¹

Abstract

Irradiation of Purines 6187 filtrates concentrated by vacuum distillation through a 14" column. The residue is subjected to vacuum distillation through a 5" column. The desired aminoalcohol distils as a viscous oil, b.p. 104-106°( 0.1 mm.), yield 56.3 g., (90.8%), re26D 1.5087. 4-Morpholino-2-butynyl N-Methylpipecolinate.-Into a 500-cc. 3-necked round bottom flask equipped with stirrer, reflux condenser, Dean-Stark water separator (CaCla tube) and heating mantle is placed a solution of 31.4 g. (0.20 mole) of methyl N-methylpipecolinate and 31.0 g. (0.20 mole) of 4-morpholino-2-butyn-l-ol in 325 cc. of re-heptane; 0.5 g. of NaOMe is added and the mixture refluxed. The methanol produced during the transesterification will separate from the heptane in the water separator. Two additional 0.3-g. portions of NaOMe may be required to complete the reaction. The reaction mixture is concentrated by slowly dis-tilling off approximately 50% of the heptane. The residue is chilled, filtered and the balance of the heptane removed by vacuum distillation through a 14" column. The residue is subjected to vacuum distillation through a 3" column. The desired ester boils at 149-151°( 0.25 mm.), yield 41.6 g. (74.3%), re26D 1.5012.4-Morpholino-2-butynyl N-Methylpipecolinate Dimethobromide.-To a solution of 14.0 g. (0.05 mole) of 4-morpholino-2-butynyl-N-methylpipecolinate (0.05 mole) in 80 cc. of isopropyl alcohol is added 19.0 g. (0.20 mole) of methyl bromide. The mixture is refluxed under anhydrous conditions for 3 hr. and then chilled. The solid is filtered off and recrystallized from the minimum amount of hot ethanol, m.p. 208-210°dec., yield 20.8 g. (88.5%).

Interaction of Deoxyinosine 3′-Endonuclease from Escherichia coli with DNA Containing Deoxyinosine

“…We have found that the binding of deoxyinosine 3Ј-endonuclease to the DNA blocks the recognition of hypoxanthine by the AlkA protein, leading to a strong inhibition of the removal of hypoxanthine by AlkA protein. 1 Therefore, based on the current biochemical data, it is unlikely that AlkA protein will be able to remove deoxyinosine from DNA when deoxyinosine 3Ј-endonuclease is present. Binding to DNA, even after nicking, indicates that deoxyinosine 3Ј-endonuclease not only acts as an endonuclease but also as a DNA binding protein.…”

“…Thus, no turnover of the enzyme cleavage activity was observed when duplex I/T or duplex I/C was used as a substrate. 1 However, deoxyinosine 3Ј-endonuclease retains nicking activity on duplex C and duplex D and exhibits a turning over of cleavage, since the enzyme cannot form stable complexes with these duplexes. One can speculate that other repair protein(s) brought to the damage site by interacting with deoxyinosine 3Ј-endonuclease in the protein-DNA complex would make an incision in the DNA 5Ј to deoxyinosine.…”

“…Deoxyinosine in DNA can arise from deamination of deoxyadenosine, which can be spontaneous or promoted by exposure of DNA to ionizing radiation, UV light, or nitrous acid (1)(2)(3). Deoxyinosine in DNA is premutagenic and can lead to A/T to C/G transition mutations (4).…”

The Photochemistry of Adenosine: Intermediates Contributing to Its Photodegradation Mechanism in Aqueous Solution at 298 K and Characterization of the Major Product

“…Superoxide ions can react with the purine peroxyl radicals forming 'OH and purine alkoxyl radica1s.j' These radicals can react further with Ado resulting in an increase in its destruction yield relative to anacrobic conditions. The reactions of the hydroxyl radical with the purines substituted at C (6) and N(9) positions have also been studied by Steenken and Vieiraj8; these researchers reported that the unimolecular transformation reaction of the O H adduct formed when hydroxyl radicals attack Ado (Eq. 13) include the opening of the imidazole moiety and the -OH elimination (dehydration process) (Eqs.…”

Deamination of Adenine by Ionizing Radiation

“…and adenylic acid to inosinic acid ( 5 ) . The ultraviolet irradiation of adenine solutions has been reported to give trace quantities of hypoxanthine ( 6 ) .…”