adenine and guanine are purines; cytosine and thymine are pyrimidines. In RNA-based
nucleotides, uracil replaces thymine. These heterocyclic bases are attached through an
N-glycosidic linkage to C1′of the ribose or deoxyribose. The phosphate group is pre-
sent as a phosphate ester and is attached at either the C5′or C3′position. Through these
various linkages, the nucleotides are assembled to form the polymeric nucleic acid.
The primary structure of DNA is the base sequence along the DNA chain that con-
tains the encoded genetic information. The secondary structure of DNA is the famous
double helix model of Watson and Crick in which two nucleic acid chains are held
together by hydrogen bonds between base pairs on opposite strands: adenine pairs with
thymine, guanine pairs with cytosine. When the two strands of the double helix coil,
two types of groove are produced, a major groove 1.2 nm wide and a minor groove
600 pm wide. In drug design, such structural data is crucial in designing anti-tumor
drugs for the treatment of cancer and in understanding the carcinogenic toxicity of flat,
polycyclic aromatic molecules.
8.1.3.1 Nucleic Acids: Biological Functions
The structure of DNA/RNA enabled Crick to formulate the “central dogma of molecu-
lar genetics.” By this dogma, three fundamental processes take place in the transfer of
genetic information. Replicationis the process by which identical copies of DNA are
made so that information can be preserved and transferred from generation to generation.
470 MEDICINAL CHEMISTRY
Figure 8.2 Nucleotide: molecular structure.