Harpers

292 / CHAPTER 33Pu/Py R O P O P OO – O –OWhere all the phosphodiester bonds are 5′ →3′, amore compact notation is possible:pGpGpApTpCpAThis representation indicates that the 5′-hydroxyl—but not the 3′-hydroxyl—is phosphorylated.The most compact representation shows only thebase sequence with the 5′- end on the left and the 3′-end on the right. The phosphoryl groups are assumedbut not shown:GGATCAOParent nucleoside triphosphatePu/Py R O P O P CH 2O – O –OOOβ,γ-Methylene derivativeOPu/Py R O P O PO – O –β,γ-Imino derivativeHNOP O –O –OP O –O –OP O –O –Figure 33–13. Synthetic derivatives of nucleosidetriphosphates incapable of undergoing hydrolytic releaseof the terminal phosphoryl group. (Pu/Py, apurine or pyrimidine base; R, ribose or deoxyribose.)Shown are the parent (hydrolyzable) nucleosidetriphosphate (top) and the unhydrolyzable β-methylene(center) and γ-imino derivatives (bottom).SUMMARY• Under physiologic conditions, the amino and oxotautomers of purines, pyrimidines, and their derivativespredominate.• Nucleic acids contain, in addition to A, G, C, T, andU, traces of 5-methylcytosine, 5-hydroxymethylcytosine,pseudouridine (Ψ), or N-methylated bases.• Most nucleosides contain D-ribose or 2-deoxy-Driboselinked to N-1 of a pyrimidine or to N-9 of apurine by a β-glycosidic bond whose syn conformerspredominate.• A primed numeral locates the position of the phosphateon the sugars of mononucleotides (eg, 3′-GMP, 5′-dCMP). Additional phosphoryl groupslinked to the first by acid anhydride bonds form nucleosidediphosphates and triphosphates.• Nucleoside triphosphates have high group transferpotential and participate in covalent bond syntheses.The cyclic phosphodiesters cAMP and cGMP functionas intracellular second messengers.• Mononucleotides linked by 3′ →5′-phosphodiesterbonds form polynucleotides, directional macromoleculeswith distinct 3′- and 5′- ends. For pTpGpTp orTGCATCA, the 5′- end is at the left, and all phosphodiesterbonds are 3′→5′.• Synthetic analogs of purine and pyrimidine bases andtheir derivatives serve as anticancer drugs either byinhibiting an enzyme of nucleotide biosynthesis orby being incorporated into DNA or RNA.REFERENCESAdams RLP, Knowler JT, Leader DP: The Biochemistry of the NucleicAcids, 11th ed. Chapman & Hall, 1992.Blackburn GM, Gait MJ: Nucleic Acids in Chemistry & Biology. IRLPress, 1990.Bugg CE, Carson WM, Montgomery JA: Drugs by design. Sci Am1992;269(6):92.