Nucleic Acids (Patrick Ch 6)

Nucleic Acids building blocks

Structure of DNA (deoxyribonucleic acid)

The primary structure of DNA is the way in which the
DNA building blocks are linked together

DNA has four building blocks, the nucleosides

deoxyadenosine, deoxyguanosine, deoxycytidine and
deoxythymidine
Each nucleoside is constructed from two components,
2-deoxyribose sugar and the bases adenine or
guanine (bicyclic purines) and cytosine or thymine
(pyrimidines)

No 1

A/Prof Joanne Jamie, CBMS306/842

No 2

Structure of DNA - Primary structure

Structure of DNA - Primary structure

the nucleoside building blocks are joined together
through phosphate groups, which link the 5-hydroxyl
group of one nucleoside unit with the 3-hydroxyl
group of the next

No 3

A/Prof Joanne Jamie, CBMS306/842

No 4

Structure of DNA - Secondary structure

Structure of DNA - Tertiary structure

the double helix is able to coil into a 3D shape =
supercoiling
during replication the double stranded DNA must
unravel but due to coiling this leads to a high level of
strain
the strain may be relieved by temporary cutting and
repairing - this is catalysed by enzymes
the quinolone antibacterial agents act on these
enzymes to prevent DNA replication
No 5

A/Prof Joanne Jamie, CBMS306/842

DNA Replication
material)

(copying

of

genetic

No 6

DNA Replication

Once the double helix unravels, a new chain can be

constructed from each of the existing DNA chains,
which act as a template
The exposed bases of the template chain H-bond with
complementary base in the form of triphosphates
The growing chain is formed with loss of diphosphate
(good leaving group)

No 7

No 8

Mechanism for growing new DNA chain

Ribonucleic acid (RNA)

primary structure similar to DNA except ribose is the
sugar (not deoxyribose) and uracil replaces thymine
HO
O

OH
HN

OHOH
ribose

N
H

uracil

base pairing occurs with adenine and uracil, and with

cytosine and guanine, however pairing is between
bases in the same chain
therefore RNA is not a double helix, but it does have
regions of helical secondary structure
No 9

Messenger RNA (mRNA), ribosomal RNA

(rRNA) and transfer RNA (tRNA)

No 10

Messenger RNA

mRNA relays the code for one particular protein from

the DNA gene to rRNA (protein production site)
i.e. the segment of DNA is copied (transcription) to
give mRNA, which then seeks out rRNA

rRNA binds to one end of mRNA, then travels along

to the other end reading the code and constructing the
protein molecule one amino acid at a time as it moves
along

tRNA links the code (triplet code) on mRNA to a

specific amino acid - different tRNA per amino acid
translation process of taking mRNA to protein
No 11

No 12

Intercalating Cytostatic Agents

Drugs acting on DNA

classified as:

intercalating drugs are compounds that are capable of

slipping between nucleic acid base pairs and
disrupting the shape of the double helix

intercalating cytostatic agents

this disruption prevents replication and transcription

alkylating agents
chain cutters

No 13

No 14

Intercalating Cytostatic Agents

Alkylating Agents

intercalators have to be flat = aromatic/heteroaromatic

alkylating agents are highly electrophilic agents that

react with nucleophiles to form strong bonds

e.g. actinomycin D and adriamycin (antibiotic and

antitumour agents) and chloroquine
N-Me-Gly
N-Me-L-Val

N-Me-Gly

L-Pro
D-Val N-Me-L-Val

NH2
L-Pro

D-Val

..
N

N-7

O
O

H3C

guanine N(7) is generally the nucleophile

O
H3C

HN

O
N

NH2

O
CH3

NH

drugs with 2 alkylating groups can

inter/intrastrand alkylation with guanines

O
CH3

undergo

Actinomycin D
No 15

No 16

Alkylating Agents

Chain cutting drugs

e.g.

bleomycin cuts strands of DNA and then prevents the

enzyme DNA ligase from repairing the damage. It
appears to act by abstracting hydrogen atoms from
DNA to form reactive radical species that fragment the
DNA

A/Prof Joanne Jamie, CBMS306/842

No 17

No 18

Drugs acting on RNA

Chain cutting drugs

Several antibiotics
translation See Ch 9

interfere

with

transcription

and

Current research is looking at oligonucleotides with

complementary nucleic acid bases to a portion of
messenger RNA = Antisense therapy

No 19

No 20

Drugs related to nucleic acids and nucleic acid

building blocks
O
HN

HO O

N3
azidothymidine

O
N

HN

HO

N
acyclovir

No 21