NUCLEIC ACID
Muhammad Wajid
Assistant Professor of Pharmaceutical Chemistry
Nucleic acid
Friedrich Miescher in 1869 isolated what he called
nuclein from the nuclei of pus cells
Nuclein was shown to have acidic properties,
hence it became called nucleic acid
The nucleic acids play a central role in the storage
and expression of genetic information
Nucleic acids are unbranched polymers of
nucleotides
History:
1869: isolated DNA from salmon sperm (Friedrich
Miescher)
1944: proved DNA is genetic materials (Avery et al.)
1953: discovered DNA double helix (Watson and Crick)
1968: decoded the genetic codes (Nirenberg)
1981: invented DNA sequencing method (Gilbert and
Sanger)
1987: launched the human genome project
2001: accomplished the draft map of human genome
Functions:
Nucleic Acid Functions:
Storage of genetic info (DNA)
Transmission of genetic info (mRNA)
Processing of genetic information
Protein synthesis (tRNA and rRNA)
Introduction:
DNA and RNA molecules are linear
polymer built from individual units called
nucleotide connected by bonds called
phosphodiester linkages
DNA and RNA are used to store and pass
genetic information from one generation
to the next
Conti……
Nucleic acid is a very large molecule made up of a
long chain of sub-units
The sub-units are called nucleotides
Each nucleotide is made up of
o A sugar called deoxyribose
o A phosphate group -PO4
o An nitrogenous base
Conti….
In both DNA and RNA molecules each
nucleotide consist of a linear backbone
that consists of repeating sugar-phosphate
units
However it is the nitrogenous bases that
are responsible for storing the genetic
information
Composition of Nucleic acid:
Sugar Component:
Although both DNA and RNA molecules
contain sugar
DNA contain a ribose sugar that lacks a
hydroxyl group on the second carbon
The absence of this –OH group stabilizes
the structure of DNA by making it more
resistant to hydrolysis
Conti…
HO
H HO
O H
O
H H
H H
H OH H OH
HO OH H
HO
Ribose Sugar DeoxyRibose Sugar
Backbone and phosphodiester linkage:
The sugar of nucleic acid are connected to one
another by 3՜- to 5՜- via a phosphodiester linkage
The –OH group on the 3rd carbon of one sugar is
connected to the –OH group on the 5th carbon of
an adjacent sugar via a phosphate group
This chain of repeating sugar-phosphate units
make up the backbone of the nucleic acid
The backbone remain constant and unchanged
Conti…
HO HO
HO
O O
O
O
O
O OH
O P
3/
P O O
O O O O
P 5/
O
O
Conti…
Phosphate group contain a negative
charge. This means that:
o In an aqueous environment these hydrophilic
regions interact with the polar molecules to
stabilizes the structure of DNA
o The Phosphodiester linkages are much less
likely to be attacked by nucleophilic agents,
which means that they are less susceptible to
O
hydrolysis Nucleophile P
O
Nitrogenous bases:
Although the backbone does not
change, the bases vary from one
nucleotide to the next
There are two categories of bases:
o Purines
o Pyrimidines
Purines consist of two fused ring
structures
Both DNA and RNA have two types of
Purines
Conti…
NH2 O
N N
N NH
N N
H N H N NH2
Adenine Guanine
Pyrimidines consist of a single ring. DNA
contain two Pyrimidines
o Thymine
o Cytosine
In RNA the thymine is replaced by uracil
Conti…
NH2 O
N NH
N O N O
H H
Thymine
Cytosine
NH
N O
H
Uracil
Conti…
The sequence of these bases is unique
to the nucleic acid
Because it is the base that vary from
nucleotide along the liner polymer
It’s the sequences of bases that
determine the genetic code
Nucleoside:
A unit consisting of a sugar molecule attached
covalently to a nitrogenous base is called a
nucleoside
Nucleosides are named by changing the
nitrogen base ending to -osine for purines
and –idine for pyrimidines
The nucleoside in RNA are:
o Adenosine
o Guanosine
o Cytidine
o Uridine
Conti…
NH2
O
N
N
N
NH
N
N
HO
N
N NH2
O
HO
H H
O
H H
H H
OH OH
H H
Adenosine OH OH
NH2 Guanosine
O
N
NH
N O
N O
HO
HO
O
H H O
H H
H H
OH OH H H
OH OH
Cytidine Uridine
Conti…
Nucleoside in the DNA are:
o Deoxyadenosine
o Deoxyguanosine
o Deoxycytidine
o Deoxythymidine
Conti…
NH2
O
N
N
N
NH
N
N
HO
N
N NH2
O
HO
H H
O
H H
H H
OH H
H H
Deoxyadenosine OH H
NH2 Deoxyguanosine
O
N H3C
NH
N O
N O
HO
HO
O
H H O
H H
H H
OH H H H
OH H
Deoycytidine Doxythymidine
Nucleotide:
Nucleotide consist of
o Nitrogenous base
o Pentose
o Phosphate
Conti…
The nucleotide in the RNA are:
o Adenylate
o Guanylate
o Cytidylate
o Uridylate
A nucleotide is a nucleoside that forms a
phosphate ester with the C5’ OH group of
ribose or deoxyribose
Conti…
NH2
O
N
N
N
NH
N
N
N NH2
N
HO
O
H H HO
O
H H H H
O OH
H H
O OH
O P O- Adenylate Guanylate
-
O P O
O-
NH2 O
O-
N NH
N O N O
HO HO
O O
H H H H
H H H H
O OH O OH
O P O- O P O-
O- O-
Cytidylate
Uridylate
Conti…
The nucleotide in the DNA are called:
o Deoxy Adenylate
o Deoxy Guanylate
o Deoxy Cytidylate
o Deoxy thymidylate
Conti…
NH2
O
N
N
N
NH
N
N
N NH2
N
HO
O
H H HO
O
H H H H
O H
H H
O H
O P O- Deoxy Adenylate Deoxy Guanylate
-
O P O
O-
NH2 O
O-
H3C
N NH
N O N O
HO HO
O O
H H H H
H H H H
O H O H
O P O- O P O-
O- O-
Deoxy Cytidylate
Deoxy Thymidylate
Conti….
Number of phosphate groups determines
nomenclature
O
Monophosphate e.g. AMP -
O P O CH2
O-
O O
Diphosphate e.g. ADP -
O P O P O CH2
O- O-
O O O
Triphosphate e.g. ATP
-
O P O P O P O CH2
O- O- O-
β-N-Glycosidic Bond:
In nucleotides the pentose ring is attached to the
nucleobase via N-glycosidic bond
The bond is formed to the anomeric carbon of the
sugar in β-configuration
The bond is formed:
o to position N1 in pyrimidines
o to position N9 in purines
This bond is quite stable toward hydrolysis,
especially in pyrimidines
Bond cleavage is catalyzed by acid
AMP, ADP and ATP:
Additional phosphate groups can be added
to the nucleoside 5’-monophosphates to
form diphosphates and triphosphates
ATP is the major energy source for cellular
activity
