Nucleic Acids

Mahpara Gondal
Pharm-D
MS pharmaceutical Chemistry

Rashid Latif College Of Pharmacy

 Objective
 Learn about
Nucleic acid
Nucleotide
Nucleoside
Basis
Importance
 Nucleic acids

 Nucleic acids are among the most important biological

macromolecules (others being amino acids-proteins, sugars-
carbohydrates, and lipids-fats).
 They are found in abundance in all living things Nucleic
acids, which include DNA (deoxyribonucleic acid) and RNA
(ribonucleic acid), are made from monomers known as
nucleotides.
 Cont…

 Each nucleotide has three components: a

5-carbon sugar, a phosphate group, and a
nitrogenous base.
 If the sugar is deoxyribose, the polymer is
DNA. If the sugar is ribose, the polymer is
RNA. When all three components are
combined, they form a nucleic acid.
Nucleotides are also known as phosphate
nucleotides.
 Components of Nucleic acid
 SUGARS
D-ribose and D-2-deoxyribose are the only sugars
so far found in the nucleic acids from which the
sugars have been isolated and identified, and they
are assumed to be the sugars universally present in
nucleic acids.
Cont…

.
 Cont…
 Both sugars are present in nucleic
acids as the β-Furanoside ring
structures as depicted below.
 Nitrogenous bases
 It has 2 types
 Pyrimidine and purine
 Pyrimidine bases found in nucleic acids are
mainly three:
• Cytosine is found both in DNA and RNA
• Thymine is found in DNA only
• Uracil is found in RNA only.
 Cont…
 Pyrimidine nucleus is represented
below.
Cont…

.
 Purine basis
 The Purine ring is more complex than
the Pyrimidine ring.
 It can be considered the product of
fusion of a pyrimidine ring with an
imidazole ring.
Cont…

.
 Cont…
 Adenine and guanine are the two
principal purines found in both DNA
and RNA.
1. Adenine
 Chemically it is 6-aminopurine.
 Cont…
2. Guanine
Chemically it is 2-amino-6-oxypurine.
 NUCLEOSIDES

The nucleosides are composed of purine

or pyrimidine base linked to either D-
ribose (in RNA) or D-2-deoxyribose (in
DNA).
 .

.
 Cont…
 They are joined by β-N-glycosidic
linkage.
 This linkage in purine nucleosides is at
position –9 of the purine base and
carbon 1’ of sugar or deoxy sugar.
 Example: Adenosine (adenine-9-
riboside)
 Cont…
 In pyrimidine nucleosides, β-N-
glycosidic linkage is formed at position
–1 of the pyrimidine base linked to
carbon –1’ of ribose or deoxyribose
sugar.
 Example: Uridine (uracil-1-riboside)
 .

.
 NUCLEOTIDES

 A nucleotide is a nucleoside to which a

phosphoric acid group has been
attached to the sugar molecule by
‘esterification’ at a definite – OH group
and thus has the general composition
base – sugar – PO4.
 Cont…
 In ribose nucleosides, there are three possible
positions for phosphate esterification namely 2’, 3’
and 5’.

 In deoxynucleosides, there are free –OH groups

only at the 3’ and 5’ positions in the deoxyribose
nucleosides. PO4 can be attached only at these
positions. The name of each nucleotide may be
derived from that of its constituent nitrogenous
base.
.

.
 Cont…
 Examples
 ATP, ADP, AMP and Cyclic AMP, GTP etc
 Functions of Cyclic AMP
Mediator of hormone action—acts as “Second
messenger” in the cell.
 • Regulates glycogen metabolism—increased cyclic
AMP produces breakdown of glycogen
(glycogenolysis).
 • Regulates TG metabolism—increased cyclic AMP
produces lipolysis (breakdown of TG).
 • Cholesterol biosynthesis is inhibited by cyclic AMP.
 • Cyclic AMP stimulates protein kinases so that
inactive protein kinase is converted to active protein
kinase.
 • Cyclic AMP modulates both transcription and
translation in protein biosynthesis.
 Cont…
 • Cyclic AMP activates different steps of steroid biosynthesis.
 • Cyclic AMP also regulates permeability of cell membranes
to water, sodium, potassium and calcium.
 • Plays an important role in regulation of insulin secretion
catecholamine biosynthesis, and melatonin synthesis.
 • Histamine increases cyclic AMP production in parietal cells
which in turn increases gastric secretion.
 • Decrease in cyclic AMP level is involved in the excitation
of bitter taste receptors in tongue.
 • Cyclic AMP plays an important role in cell differentiation.
Addition of cyclic AMP to malignant cell lines in vitro
reduces growth rates and restores their morphology to normal
 DEOXYRIBONUCLEIC ACID (DNA)

 DNA is a polymer of
deoxyribonucleotides and is found in
chromosomes, mitochondria an
chloroplasts.
 The nuclear DNA is found bound to
basic proteins called histones. DNA
is present in every nucleated cell and
carries the genetic information. It is
conveniently isolated from viruses,
thymus gland, spleen, leucocytes, etc.

Chemistry
Histones are a small family of closely related basic proteins in
chromatin.

 four types of histones.

They are—
 H2A, H2B, H3 and H4, called core histones.
 The structure of all four types of histones are highly conserved
between species. This extreme conservation implies that the
function of histones is identical in all eukaryotes.

 Structure: The –COOH terminal 2/3rd of the molecules have a

typical random amino acid composition, but 1/3rd of the –NH2
terminal are rich in basic amino acids.

 Interaction of histones: The four types of histones interact with

each other in very specific ways as follows:
 H3 and H4 form a tetramer containing 2 molecules of each (H3H4)2
 H2A and H2B form dimers (H2A–H2B).
,
 Cont…
 In the nucleosome, the DNA is
supercolied in a left hand helix over the
surface of the disc-shaped histone
octamer.

 Function: This association of histone

octamer with DNA protects the DNA
from digestion by a nuclease.
 Primary Structure of
DNA
 Chromosomal DNA consists of very long DNA
molecules.
 Each DNA is a polymer of about 1010
deoxyribonucleotides.
 Normally there are only four different types of
deoxyribonucleotides that are found in DNA
molecule, namely,
 1. adenine deoxyribonucleotide(dA),
 2. thymine deoxyribonucleotide (dT),
 3. guanine deoxyribonucleotide (dG), and
 4. cytosine deoxyribonucleotide (dC).
 .

..
 Cont…
 Nucleotides of each of the two helical strands are
bound to each other by covalent 3’-5’
phosphodiester linkage.
 Each such bond is formed by the ester linkages of
a single phosphate residue with the 3’ –OH (i.e.
C – 3’ –OH group of the ribose sugar) of one
nucleotide with the C – 5’ –OH group of ribose
of the next nucleotide.
 This kind of bonding gives rise to a linear
polydeoxyribonucleotide strand with 2 free ends
on both sides.
.
 Cont…
 The primary structure is the number and
sequence of different deoxyribonucleotides in its
strands joined together by phosphodiester
linkages.
 The backbone of the primary structure is the
linear strand of interconnected sugar phosphate
residues while the purine or pyrimidine
connected with the sugar residue projects
laterally from the backbone.
 (b) Secondary Structure of DNA

 This consists of a double stranded

helix formed by the two
polydeoxyribonucleotide strands
around a central axis. This type of
model was first proposed by Watson
and Crick
 Cont…
 DNA is a double helix. Each of its two
strands is coiled about a central axis,
usually a right handed helix.
 The two sugar phosphate backbones
wind around the outside of the bases like
the banisters of a spiral staircase and
are exposed to the aqueous solution.
 The phosphodiester bonds in the
two interwoven strands run in
opposite directions. Therefore the
strands are called antiparallel.
 Cont…
 Thus the polarity of the two strands will
be 3’ – 5’ and 5’ – 3’. The 3’ – 5’
strand is called coding or “template
strand” and 5' – 3' strand is called
noncoding‘strand
 Cont…
 The aromatic rings of bases are hydrophobic and
they are stacked in the interior, nearly
perpendicular to the long axis of the helix.
 Adenine base of one strand of DNA is hydrogen
bonded to a thymine in the opposite strand;
while the guanine is hydrogen bonded to a
cytosine.
 Denaturation of DNA

 Two strands of DNA double helix can separate or

unwind during processes such as DNA
replication, RNA transcription and genetic
recombination.
 Complete unwinding of DNA can take place in
vitro and is called denaturation of DNA or it is
also known as a helix to coil transition.
 Cont…
 The melting temperature of DNA is determined by
its base composition. Since there are two hydrogen
bonds between A and T while three between G and
C, increasing G-C base pairs raises Tm.
 Tm is strongly influenced by the base composition
of the DNA.
 DNA rich in G-C pairs has a higher Tm than DNA
with high proportion of A-T pairs.
 Mammalian DNA, which has about 40 per cent G-C
pairs, has a Tm of about 87°C.
 Annealing:
 Once the strands are separated, they can be
renatured. If a melted sample of DNA is slowly
cooled, the absorbance of the solution decreases.
This is indicative of complementary strands
being paired again.
 This process is called as annealing. Annealing
can occur only at a temperature below Tm of
DNA which is about 70oC.
 It is fastest at 20oC below Tm or 50oC.
 RIBONUCLEIC ACID
(RNA)

 Ribonucleic acid is a polymer of ribonucleotides

of Adenine, Uracil, Guanine and Cytosine, joined
together by 3’ – 5’ phosphodiester bonds.
 Thymine is absent in RNA. RNA is found in the
nucleolus, ribosomes, mitochondria and
cytoplasm.
 Cont…
 Structures of RNA
 (a) Primary Structure of RNA

The primary structure of RNA is defined as the

number and sequence of ribonucleotides in the
chain.
 •Each linear strand is held together by the
ribonucleotides bound to each other by 3’,–5’
phosphodiester bonds joining 3’–OH of one
nucleotide with the 5’–OH of the next
 Cont…
 Secondary Structure of RNA
 The secondary structure of RNA involves various
coil formation of the polyribonucleotide chain.
 These coil structures are stabilised by
hydrophobic interactions between the purine and
pyrimidine bases.
 Cont…
 Tertiary Structure of RNA
 The tertiary structure of RNA involves
the folding of the molecule into three-
dimensional structure.
 The crosslinking also occurs at various
sites stabilised by hydrophobic and
hydrogen bonds producing a compactly
coiled globular structure.
 Cont…
 Types of RNA
 There are mainly three types of RNA
found in human beings. These are:
 1. Messenger RNA or m-RNA,
 2. Transfer or soluble RNA or t-
RNA, and
 3. Ribosomal RNA or r-RNA.
 The main function of each of these
RNA is protein synthesis.
 Cont…
 In human cells there are small nuclear RNA or
Sm-RNA which are not involved in protein
biosynthesis directly. They may have some role
in processing of RNA and cellular architecture.
They are found in nucleoplasm, nucleolus,
perichromatic granules, and cytoplasm and vary
in size from 90 nucleotides to 300 nucleotides.
large precursor of m-RNA called as
heterogeneous nuclear RNA or hn-RNA is also
found in the nucleus
 Messenger RNA (m-RNA)

 This is the most heterogeneous class of RNA

with respect to its size and stability. The
molecular weight varies from 3 × 104 to 2 × 106.
They consist of 103 to 104 ribonucleotides.
 It carries mainly adenine guanine, cytosine and
uracil as the major bases and methylpurines and
methylpyrimidines as minor bases.
 Transfer RNA or t-RNA

 These are also called as soluble or s-RNA. They

remain largely in cytoplasm. The t-RNAs are
relatively small, single-stranded, globular
molecules with molecular weight of 2 to 3 × 104.
There are at least 20 different t-RNA molecules.
 (a) Primary structure of t-RNA: t-RNA molecules
consist of approximately 75 nucleotides. Their
bases include adenine, guanine, cytosine, uracil,
pseudouridine (ψ) or uracil 5-ribofuranoside and
thymine are present in one loop.
 Cont…
 Secondary structure of t-RNA: Each single
stranded t-RNA molecule remains folded to form
a clover-leaf secondary structure. These folds of
the secondary structure are stabilized by H-bonds
between complementary bases in different
portions of the same strand. These double
stranded helical structures are called as stems.
 (c) All t-RNA molecules contain 4 main arms or
loops:
 .

.
 Cont…
 Ribosomal or r-RNA
 A ribosome is present in the cytoplasm and is a
nucleoprotein. It is on the ribosome that the m-
RNA and r-RNA interact during the process of
protein biosynthesis. The r-RNA forms 80 per
cent of the total cellular RNA.
 Cont…
 The function of r-RNA in ribosome particle is
still not clearly understood. However, they are
necessary for ribosomal assembly and seem to
play key roles in the binding of m-RNA to
ribosomes and its translation.
 Similarities between DNA and RNA

 1. Both have adenine, guanine, cytosine.

 2. The nucleotides are linked together by
phosphodiester bonds.
 3. The bonding is in 3’– 5’ direction.
 4. Main function involves protein biosynthesis
 Cont…
Differences
1. In addition to A, G, C, the fourth base is
1. In addition to A, G, C, the fourth base is U
T—Uracil absent —Thymine absent
2. Pentose sugar is deoxyribose 2. Pentose sugar is ribose
3. Present in nucleus, mitochondria but
3. In addition to nucleus, RNA is found in
never in cytoplasm cytoplasm
4. They consist of 2 helical strands 4. Single stranded
5. There are A, B, C, D and E forms of5. There are t-RNA, m-RNA, r-RNA, hn-
DNA RNA and SnRNA
6. Large molecules 6. Only hn-, m- and r-RNA are large
molecules
7. One strand 3’ – 5’ carries genetic 7. m-RNA transcribed from DNA carries
information genetic information.
8. DNA can form RNA by the process of 8. RNA cannot give rise to DNA under
“transcription” normal conditions, but it can under special
experimental conditions using reverse
transcriptase

9. Purine and pyrimidine contents are 9. Not equal

almost equal.