Publisher Summary This chapter explains the chemistry of guanine and its biologically significant derivatives. The position of guanine as an essential component of the genetic material of all living organisms has lent great importance to the study of its chemistry. A number of misconceptions have arisen in the past because of faulty analogies between guanine and benzenoid systems and this has led to the use of incorrect structures, such as enol tautomers and protonated amino groups. There is now at hand a considerable amount of information concerning a number of the transformations of the guanine molecule, but many others are undoubtedly still awaiting discovery. A major challenge is to devise reagents capable of modifying under physiological conditions a single component of the nucleic acids, such as guanine. Such reagents could help in determining base sequences by facilitating or inhibiting specific cleavages, changing enzymatic specificities, or acting as markers visible with the electron microscope. Other reagents might serve as mutagens and be valuable adjuncts to genetic studies.

Chemistry of guanine and its biologically significant derivatives.

Chemoselective formation of glycoconjugates from unprotected glycans is needed to further develop chemical biology involving glycans. Carbohydrate oxime formation is often slow, and organocatalysis by anilines would be highly promising. Here, we present that carbohydrate oxime formation can be catalyzed with up to 20-fold increases in overall reaction rate at 100 mM aniline. Application of this methodology provided access to complex glycoconjugates.

Nucleophilic catalysis of carbohydrate oxime formation by anilines.

Kinetic study of the reaction of sulfamethoxazole and glucose under acidic conditions: I. Effect of pH and temperature.

A new type of interstrand cross-link resulting from the reaction of a DNA abasic site with a guanine residue on the opposing strand of the double helix was recently identified, but the chemical connectivity of the cross-link was not rigorously established. The work described here was designed to characterize the chemical structure and properties of dG-AP cross-links generated in duplex DNA. The approach involved characterization of the nucleoside cross-link "remnant" released by enzymatic digestion of DNA duplexes containing the dG-AP cross-link. We first carried out a chemical synthesis and complete spectroscopic structure determination of the putative cross-link remnant 9b composed of a 2-deoxyribose adduct attached to the exocyclic N(2)-amino group of dG. A reduced analogue of the cross-link remnant was also prepared (11b). Liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis revealed that the retention times and mass spectral properties of synthetic standards 9b and 11b matched those of the authentic cross-link remnants released by enzymatic digestion of duplexes containing the native and reduced dG-AP cross-link, respectively. These results establish the chemical connectivity of the dG-AP cross-link released from duplex DNA and provide a foundation for detection of this lesion in biological samples. The dG-AP cross-link in duplex DNA was remarkably stable, decomposing with a half-life of 22 days at pH 7 and 23 °C. The intrinsic chemical stability of the dG-AP cross-link suggests that this lesion in duplex DNA may have the power to block DNA-processing enzymes involved in transcription and replication.

/pdf/chemical-structure-and-properties-of-interstrand-cross-links-2omyxvxk2d.pdf

Brian E. Connett

Papers

The mechanism of the hydrolysis of N-aryl-D-glucosylamines.

The mechanism of the hydrolysis of -aryl glucosylamines

The structure of some -aryl glucosylamines