Q6(e). Nucleosides, nucleotides; primary structure of DNA and RNA

Introduction. Nucleic acids are polymers of nucleotides. A nucleoside = nitrogenous base + pentose (linked by a β-N-glycosidic bond from N-9 of a purine or N-1 of a pyrimidine to C-1' of the sugar). A nucleotide = nucleoside + phosphate ester, usually at the 5'-OH.

Scheme: Base on C-1' (β); phosphate on C-5'; DNA sugar lacks the 2'-OH.

1. Bases: purines adenine (A) and guanine (G); pyrimidines cytosine (C), thymine (T) (DNA) and uracil (U) (RNA).
2. Sugars: 2'-deoxy-D-ribose in DNA, D-ribose in RNA (furanose form).
3. Nucleosides: adenosine, guanosine, cytidine, uridine (RNA); deoxyadenosine, deoxyguanosine, deoxycytidine, thymidine (DNA).
4. Nucleotides: 5'-monophosphates (AMP, dAMP, …); also di- and triphosphates (ATP).

Primary structure

1. Nucleotides are linked by 3',5'-phosphodiester bonds: the 3'-OH of one sugar and the 5'-OH of the next are esterified by one phosphate. This gives a sugar–phosphate backbone with the bases as side groups.
2. The primary structure is the sequence of bases, written from the 5' end (5'-phosphate) to the 3' end (3'-OH), e.g. 5'-pA-G-C-T-3'. It carries the genetic information.
3. Each phosphodiester carries one negative charge at pH 7, so nucleic acids are polyanions.
4. DNA vs RNA: DNA has deoxyribose and T; RNA has ribose and U. The 2'-OH of RNA attacks the neighbouring phosphate in alkali, so RNA is hydrolysed by base while DNA is stable; DNA is usually double-stranded, RNA single-stranded.

Conclusion. Nucleoside = base + (deoxy)ribose; nucleotide = nucleoside phosphate. The primary structure of DNA and RNA is the 5'→3' base sequence on a 3',5'-phosphodiester backbone; DNA uses deoxyribose and A, G, C, T, RNA uses ribose and A, G, C, U.

Application. Nucleoside analogues such as AZT (zidovudine) and acyclovir, which lack a usable 3'-OH, stop viral DNA chain growth and are used as antiviral drugs.