Fundamentals of Medicinal Chemistry

O

H

HH

H

HO N

N N

N

NH 2

O CH 2

OH

P

O

O

−O

O P

OH

O−

O

H

HH

OH

H

N

N N

N

NH 2

P O P O CH 2

O

−O

O

−O

P O

O

−O

−O

H

O

H

HH

OH

H

N

N N

N

NH 2

P O P O CH 2

O

−O

O

−O

P O

O

−O

−O

OH

Deoxyadenosine triphosphate (dATP)

Adenosine triphosphate (ATP)

Adenosine 3',5'-diphosphate (3',5'-ADP)

Figure 1.29 Some examples of individual nucleotides. The abbreviations used to represent the

structures of nucleotides based on deoxyribose are prefixed byd-

1.6.2 DNA, structure and replication

DNA molecules are large, with RMMs up to one trillion (10

12

). Experimental

work by Chargaff and other workers led Crick and Watson to propose that the

three dimensional structure of DNA consisted of two single molecule polymer

chains held together in the form of a double helix by hydrogen bonding between

the same pairs of bases, namely the adenine–thymine and cytosine–guanine base

pairs (Figure 1.30). These pairs of bases, which are referred to ascomplementary

base pairs, form the internal structure of the helix. They are hydrogen bonded in

such a manner that their flat structures lie parallel to one another across the

inside of the helix. The two polymer chains forming the helix are aligned in

opposite directions. In other words, at the ends of the structure one chain has a

free 3’-OH group whilst the other chain has a free 5’-OH group. X-Ray diffrac-

tion studies have since confirmed this as the basic three dimensional shape of the

polymer chains of the B-DNA, the natural form of DNA. This form of DNA

has about 10 bases per turn of the helix. Its outer surface has two grooves,

known as the minor and major grooves respectively, which act as the binding

sites for many ligands.

Electron microscopy has shown that the double helical chain of DNA is

folded, twisted and coiled into quite compact shapes. A number of DNA

28 BIOLOGICAL MOLECULES