Nucleic Acids (Patrick Ch 6)

No 1

RNA & DNA structure & intro to function

Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)

carriers and processors of cells genetic information
DNA is found predominantly in the nucleus of the cell
RNA is found mainly outside of the nucleus in the cytoplasm
(different types depending on roles)
Coded in a cells DNA is all the information that determines the
nature of the cell, controls the cells growth and division and
directs the biosynthesis of enzymes and other proteins required
for cellular functions
DNA stores the genetic and protein information, RNA transcribes
and translates the information for protein synthesis

No 2
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 3

Nucleic Acids building blocks

No 4
A/Prof Joanne Jamie, CBMS306/842
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 5

Nucleotide =
Nucleoside phosphate
Structure of DNA - Primary structure

No 6
A/Prof Joanne Jamie, CBMS306/842
Structure of DNA - Secondary structure

Purine and pyrimidine pairing give

constant diameter

Base pairs are stacked

Polar groups outside
No 7
A/Prof Joanne Jamie, CBMS306/842

DNA structure

http://www.youtube.com/watch?v=ZGHkHMoyC5I

No 8
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 9

DNA Replication (copying of genetic

material)
DNA replication occurs in all living organisms and
copies their DNA must happen prior to cell division
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 10
DNA Replication

No 11

Mechanism for growing new DNA chain

No 12
DNAs role

DNA contains the genetic information that allows all

modern living things to function, grow and reproduce
If stop replication stop cell growth and division
DNA also codes for proteins

No 13

Ribonucleic acid (RNA)

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

O N
OHOH H

ribose 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 14
Messenger RNA (mRNA), ribosomal RNA
(rRNA) and transfer RNA (tRNA)
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 15

Messenger RNA

No 16
Transcription - Messenger RNA

No 17

No 18
 No 19

Translation of RNA protein synthesis contd

No 20
Drugs acting on DNA

classified as:
intercalating cytostatic agents
alkylating agents
chain cutters

No 21

Intercalating Cytostatic Agents

intercalating drugs are compounds that are capable of
slipping between nucleic acid base pairs and
disrupting the shape of the double helix
this disruption prevents replication (no new cells) and
transcription (no protein vital for cell function)

No 22
 Intercalating Cytostatic Agents
Consider how proflavine works chemically

No 23

Intercalating Cytostatic Agents

intercalators have to be flat = aromatic/heteroaromatic
e.g. actinomycin D and adriamycin (antibiotic and
antitumour agents) and chloroquine
N-Me-Gly N-Me-Gly
L-Pro L-Pro
N-Me-L-Val
D-Val N-Me-L-Val D-Val
O O
O O
H3C HN H3C NH
O
O

N NH2

O O

CH3 CH3

Actinomycin D

No 24
 Function in Nucleic Acids. Guanine, like other nitrogenous bases, can be part of
a nucleotide; this means it's attached to a sugar and one or more phosphates.
DNA and RNA are both nucleic acids, made of nucleotides chained together. ...
Guanine bonds to cytosine because they both share three hydrogen bonds.

Alkylating Agents
alkylating agents are highly electrophilic agents that
react with nucleophiles to form strong bonds
guanine N(7) is generally the nucleophile
NH2
.. N-7
N
N

N N

drugs with 2 alkylating groups can undergo

inter/intrastrand alkylation with guanines

No 25

Alkylating Agents
e.g.

No 26
A/Prof Joanne Jamie, CBMS306/842
 Chain cutting drugs

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

Bleomycin is a type of antibiotic that is poisonous to cells. It binds to the cancer cells' DNA so that
the cells can't divide or grow. It also causes free radicals to be made inside the body. Free radicals
are overactive oxygen atoms that damage DNA

No 27

Chain cutting drugs

No 28
Drugs acting on RNA

Several antibiotics interfere with transcription and

translation See Ch 9
Current research is looking at oligonucleotides with
complementary nucleic acid bases to a portion of
messenger RNA = Antisense therapy

No 29

Drugs related to nucleic acids and nucleic acid

building blocks
O

HN
Used for treatment of
HO O N HIV/AIDS infection
O

N3

azidothymidine

O
N One of the most commonly used antiviral drugs
HN
N
primarily used for the treatment of herpes
O
N simplex virus infections, chickenpox, shingles
HO acyclovir

No 30
Mechanism for growing new DNA chain

HN

HO O N

N3

azidothymidine

O
N
HN
N
N
HO O acyclovir

No 31