Chemistry of nucleic acids and their constituents

Complete hydrolysis of nucleic acids (see Section 3.4) by chemical or enzymatic means liberates the nucleic acid building blocks phosphate, sugar (ribose or deoxyribose), and bases, in a 1 1 1 ratio. Depending on the conditions of the hydrolysis, larger compounds containing these building blocks are obtained (oligonucleotides). 

All bases found in nucleic acids are derivatives of purine or pyridine. Only in some nucleoside antibiotics is an exchange of a carbon atom for a nitrogen atom, or vice versa, observed. The common bases are adenine 6-amino-purine guanine 2-amino-6-ketopurine cytosine 2-keto-4-aminopyrimidine uracil 2,4-diketopyrimidine and thymine (in DNA) 2,4-diketo-5-methylpyrimidine (5-methyluracil). Minor components found in various DNA and RNA are 5-methylcy-tosine, 5-hydroxymethylcytosine, 5-hydroxymethyluracil, 6-methylaminopurine, 5,6-dihydrouracil (in tRNA) and numerous other methylated bases (in tRNA). The bases are quite resistant to oxidation but easily attacked by nucleophilic reagents. In particular, the positions meta to the nitrogen atoms have low electron densities. Substitutions by electron donors (amino, methyl, hydroxyl) facilitate nucleophilic substitution on the other atoms. 

If a base is linked through the N of the pyrimidines or the N of the purines with the Ci of the sugar moiety, (jS-D-ribofuranose in RNA or jS-D-2 -deoxyribofuranose in DNA), one obtains the nucleosides. This substitution will change the behavior of the base considerably the solubility in water increases and that in aprotic solvents decreases. Con- 

Another naturally occurring sugar in nucleosides is arabi-nose. The arabinosides inhibit many nucleic acid enzymes and have widespread therapeutical applications. Some bases, nucleosides, and nucleotides, with indications of their protonation sites, are listed in Fig. 3.1. The abbreviations used are found in the Appendix. 

The structure and conformation of a nucleoside is determined by a variety of factors ionization state, solvation, external influences (ions, cofactors, etc.), and temperature. All these parameters must be controlled so that conformation and, therefore, the behavior of these compounds, can be understood. We shall treat these points in some detail. 

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