Pyrimidines (Py, Y)
Conformation of nucleic acid components
Rotation around the N-C glycosidic bond
The building blocks of nu cleic acids are nucleotides, which are the phosphate esters of
nucleosides. These are formed by condensation of a base and a pentose. In RNA, the pentose is
D-ribose and is linked in its furanose form from C’-1 to N-9 of a purine, adenine, or guanine, or N-
1 of a pyrimidine, cytosine or uracyl. In DNA, 2-deoxy-D-robose is j oined in th e same way to the
four bases, among which thymine takes place of uracyl. The phosphate esters are strong acids
and exist as anions at neutral pH. The “bases” are, in reality, only very weakly basic and A, C,
and G b ecome protonated only below pH 4. The amide NHs in G, T, and U a re deprotonated at
pHs above 9.
Hydrogen bond s can be formed between the majo r amino-keto tauto mers of the bases to link A with T
and C with G in Watson-Crick base-pairing. Such hydrogen bonds are larg ely electrostatic in character.
“Wobble” and Hoogsteen base-pai rs offer minor variations to Watson-Crick pairing, and are seen in tRNA
Nucleotides have defined shapes with a g eneral preference for the anti-confo rmers of th e glycosylic
bond , fo r the C4’-C5’ bond s , an d for the two C-O(P) bonds and . The furanose ring is puckered to
relieve strain and can adopt either the C2’-endo or the C3’-endo conformatio n, which are in rapid
equil ibrium at room temperature.
Hydrolysis on nucleic acids
gives 3’ and 5’
(implies 3’-5’ phosphodiester
A-T (T-A) and G-C (C-G) base pairs have the same geometry
The primary structure of DNA has a string of nucleosides, each join ed to it s neighbors through
phosphodiester bond s. Each 5’-hydroxyl group is link ed through a phosphate to a 3’-hydroxyl group. Thus,
the uniqueness of any primary structure depends on the sequence of the bases only .
A-DNA and B-DNA are the major standard DNA secondary structures with right -hand ed double helices
and Watson-Crick base-pairing.
A-DNA has 11 residues per turn, the bases are tilted 20o to enhance stacking, and they lie 4.5A away from
the axis. As a result, A-DNA helix is s tiff and shows little sequence-dependent variatio n in structure. The
major g roove is deep and narrow, the minor g roove broad and shallo w.
B-DNA has 10 bases per turn with no tilting of the bases. The wide major groove and narrow minor groove
are of the similar depth, and both grooves are solvated. The structure is flexibl e to permit confo rmational
chang es in the backbone in response to different local sequences.
Z-DNA is left-ha nded helix stabi lized by high concentrations of salt. It is most favored for alternating GC
sequences. Watson-Crickpairing remain s, but the purines adopt the syn-glycoside and the C3’-endo sugar
pucker. The phosphate backbone has a zig-zag appearance. The mino r groove is very narrow and d eep; the
major g roove is very shallo w.