Fundamentals of Medicinal Chemistry

Sugar

Sugar

Sugar

O

P

O

O

P

−O O

O

Sugar

Sugar

−O O

Sugar

C

O

P

T

O

O

G

P

−O O

O

−O O

G

A

C

Minor

groove

Major

groove

Major

groove

Minor

Bases groove

Bases

Bases

CH 3

NN

O

O

N

H H

H

N

N

N

N

N

N

N

O

N

N

N

H

H

N

H

O

H

N

H

Deoxyribose

residue

Deoxyribose

residue

Deoxyribose

residue

Deoxyribose

residue

A-T base pair G-C base pair

5' End 3' End

Figure 1.30 The double helical structure of B -DNA. Interchanging of either the bases of a base

pair and/or base pair with base pair does not affect the geometry of this structure. Reproduced by

permission of Prentice Hall fromChemistry for Pharmacists and the Life Sciencesby G Thomas

structures are cyclic, and these compounds are also coiled and twisted into

specific shapes. These shapes are referred to as supercoils, supertwists and

superhelices as appropriate.

DNA molecules are able to reproduce an exact replica of themselves. The

process is known as replication and occurs when cell division is imminent

(Figure 1.31). It is believed to start with the unwinding of the double helix

starting at either the end or more usually in a central section, the separated

strands acting as templates for the formation of a newdaughterstrand.New

individual nucleotides bind to these separated strands by hydrogen bonding to

the complementary parent nucleotides. As the nucleotides hydrogen bond to the

parent strand they are linked to the adjacent nucleotide, which is already

hydrogen bonded to the parent strand, by the action of enzymes known as

DNA polymerases. As the daughter strands grow the DNA helix continues to

unwind. However,bothdaughter strands are formed at the same time in the 5’to

3 ’direction. This means that the growth of the daughter strand that starts at the

NUCLEIC ACIDS 29