Chemistry of DNA &

RNA
Complete hydrolysis of Nucleic acids—

Nitrogen Bases
Purines & Pyrimidines
A Sugar Component
Phosphoric Acid

Partial Hydrolysis
Nucleosides
(Base + Pentose sugar)
Nucleotides
(Base + Pentose sugar + Phosphoric acid)
Nitrogenous Bases
Purines
Pyrimidines

Purine Bases
Two ringed structures having 9,N & C atoms in
cyclic forms
Derivatives of the parent compound Purine
Fusion of a pyrimidine ring & imidazole ring
Both types of nucleic acids contain same purine
bases Adenine & Guanine
 6
N7
N1 5
8
2 4
3 9
N N
H

PURINE
 O
NH2
6
6 N7
N7
N1 5
HN 1 5
8
8
2 4
2 4 3 9
3 9
NH2 N N
N N H
H

ADENINE GUANINE
6-AMINO PURINE 2-AMINO -6-OXO-PURINE
Pyrimidine Bases
Derivatives of six membered parent ring compound
Pyrimidine

N3 5

2
6
1
N
PYRIMIDINE

Cytosine – in both types of nucleic acids

Uracil – in RNA
Thymine – in DNA
 NH2 O

4 4
N3 5
N3 5 CH3
2 2
6 6
1
O o 1
N O
N
H 4
CYTOSINE N3 5 THYMINE
4-AMINO, 6-OXO PYR 2,4- DIOXO-5-METHYL PYR
2
6 5-METHYL URACIL
1
O N
URACIL
2,4.DIOXO PYR
Modified Bases

DNA & RNA bases are substituted by different

groups
They are derivatives of nitrogenous bases
Also called minor bases
Modified Bases present in DNA

Methylated forms of the major bases

In some viral DNAs , certain bases may be
hydroxymethylated or glucosylated
Generally these modified or unusual bases have
roles in regulating or protecting the genetic
information NH2
 5-methyl cytosine
 involved in gene regulation 4
in eukaryotes. N3 5 CH₃
 Abundant in wheatgerm DNA. 2
6
1
O N
5-hydroxy methyl cytosine
T-even bacteriphages (T2, T4, T6) & PBS1 etc.
T-even phages infect bacterium E.coli
 PBS1 (uracil replaces thymine) attacks Bacillus
subtilis
In T phages & PBS1, 5-hydroxymethyl cytosine
replaces cytosine NH2
the hydroxl group of the
former base can be 4
further glucosylated. N3 5 CH₂ OH
2
6
1
O N
GLUCOSYLATED
N²- methylguanine N⁶-methyl adenine

O NH-CH₃
6
6 N7
N7
N1 5
HN 1 5 8
8
2 4
2 3 9
4
3 9
N N
H₃C-HN N N H
Modified bases present in RNA

RNA especially tRNA has many modified bases

wherein methyl group, acetyl group, oxo group may
be attached
The various modified bases in RNA are:

1- methyl adenine

2- methyl adenine
6- methyl adenine
6,6- dimethyl adenine
2- methyl thio-6- isopentenyl adenine
1- methyl guanine
2- methyl guanine
2,2- dimethyl guanine
2,2,7- trimethyl guanine
xanthin
Hypoxanthin
Dihydro uracil
5- hydroxy uracil
5- methyl uracil (thymine)
2- thiouracil
3- methyl uracil
3- methyl cytosine
5- methyl cytosine
5- hydroxymethyl cytosine
4- acetyl cytosine
In addition to these bases one uncommon base y-
base is also present
Found mostly in tRNA & is modified guanine
CH₃-- O-- CO CH NH– CO– O-- CH₃
CH2
CH2
N
N

N N N Y- base
(Wybutosine)
CH₃
Pentose and deoxypentose sugars

The main sugar component of RNA is D- ribose

 in polynucleotides occur in D- ribofuranose form
In DNA, the sugar is 2- deoxyribose which also occur
in D- furanose form
The sugar in both RNA & DNA is in the β- furanose
form
Pentose & deoxypentose Sugars

O 5’ O
5’
OH CH2OH OH
CH2OH
1’
1’ 4’
4’
H H
H H H H 3’ 2’ H
H 3’ 2’

OH OH OH H
β- D- ribofuranose β -D-2-deoxyribofuranose
The pentose ring is not planar but occurs in one of a
variety of conformations generally described as “
puckered”

CH2OH
O OH

H H H
H

OH OH

Ribofuranose ring in polynucleotides can exist in

four different puckered conformations
In all these cases, four of the five C- atoms are in a
single plane
The fifth atom C-2’ or C-3’ is on either the same or
the opposite side of the plane relative to the C-5’
atom

If on the same side, it is called as endo (C-2’ endo or

C-3’ endo)

If on the opposite side of the plane, it is called as

exo (C-2’ exo or C-3’ exo)
 Base
C-2’ endo

C-2’ exo
C-3’ endo

Base

C-3’ exo
DNA & RNA have two distinctions:
Different pentoses
Presence of uracil in RNA & thymine in DNA

It is the presence of pentose sugar that defines the

identity of a nucleic acid

If the nucleic acid contains 2’-deoxy-D-ribose, it is

DNA even though it may contain some uracil

If the nucleic acid contains D-ribose it is RNA

regardless of its base composition
Nucleosides
Purine or Pyrimidine base linked to a ribose or
deoxyribose sugar

Linkage between the base and the sugar is N-

glycosidic linkage

In Purines the linkage is N9-1’

In Pyrimidines the linkage is N1-1’

 NH₂ NH₂
6 6
N7 N7
N1 5 N1 5
8 8
2 4 2 4
3 9 3 9
N N N N
O O
CH₂OH CH₂OH

H H H H
H H H H

OH OH OH H

Adenosine deoxyadenosine
 O O

N N
HN HN

9 9
NH₂ N N NH₂ N N
O O
CH₂OH CH₂OH
1’ 1’

H H H H
H H H H

OH OH OH H

Guanosine Deoxyguanosine
 NH₂
NH₂

N
N
1
O N 1
O N
O
CH₂OH O
1’ CH₂OH
1’
H H
H H H H
H H
OH OH
OH H
Cytidine Deoxycytidine
 o O

HN HN CH₃

1 1
O N O
N
O
O CH₂OH
CH₂OH
1’
1’
H H
H H H H
H H

OH H
OH OH
Uridine Thymidine
 Evidences to show that the linkage between
pyrimidines and sugars is N1-1’C:

Hydrolyse cytidine with HNO₂ it is deaminated &

is converted into uridine
 NH₂ O

N HN

1 1
O N O N
O
CH₂OH O
HNO₂ CH₂OH
1’
1’
H H
H H H H
H H

OH OH
OH OH
Cytidine Uridine
 This shows that the 4th position is free & can be
easily deaminated

Similarly positions 2nd & 3rd can be easily

methylated or hydroxylated

So these positions can’t be involved in glyosidic

linkage they are free
When a nucleoside is treated with hydrazine it
modifies positions 5th & 6th

Only the position 1 remains unchanged

This shows that sugar can be attached only at

position 1
 Sugars which have free carbonyl group at
position 1 get easily reduced

Ribose can be attached to the base at any

position but it is found that nucleosides have non
reducing properties
This shows that the CHO group at 1’ position of
pentose sugar is not free

It is involved in glycosidic linkage

Hence it confirms that the linkage is N1-1’C

 Evidences to show that the linkage between
purines & sugars is N9-1’C

Nucleosides have non reducing properties this

shows that the 1’C of sugar is involved in the
glyosidic linkage

The hydrolyzing conditions are different for

different bonds

The C-N bond requires mild hydrolysis & C-C

bond requires strong conditions for hydrolysis
This shows that linkage can be only at positions
1,3,7 & 9 since mild hydrolysing conditions are
required for purine nucleosides

Positions 1 & 3 can be easily methylated or

hydroxylated thus they are not involved in the
glycosidic linkage

For positions 7 & 9 , the absorption spectrum of

7- methyl adenine & 9-methyl adenine were
compared with that of adenosine
Spectrum of 9- methyl adenine closely
resembles the adenosine spectrum

This proves that the linkage is N9-1’C

glycosidic linkages other than N1-1’C & N9-1’C
o
The nucleoside 5-β-D-
HN ribofuranosyl uracil has
been obtained in small
1 amounts from the
O N digestion products of
H RNA ,particularly tRNA
O
CH₂OH This has been named as
1’
pseudouridine
H H In this case the linkage is
H H
C5-1’C instead of N1-1’C
OH OH
 O

N
HN

9
NH N N
O H
HOH₂C
1’

H H
H H

OH OH
2-riboguanine
Nucleotides:

Phosphoric acid esters of nucleosides

Derived from ribonucleosides – ribonucleotides
deoxyribonucleosides-- deoxyribonucleotides
 NH₂
6
N7
N1 5
8
2 4
3 9

Oˉ N N
O
P O H₂C
Oˉ

O H H
H H

OH OH

AMP Adenosine mono phosphate Adenylic acid

 O

N
HN

Oˉ NH₂ N N
O
P O H₂C
Oˉ 5’ 1’

H H
O H H

OH OH

GMP Guanosine monophosphate Guanylic acid

 NH₂

Oˉ
O N
O
Oˉ P O H₂C
1’

O H H
H
H

OH OH

CMP Cytidine monophosphate Cytidylic acid

 o

HN

Oˉ
O N
O
Oˉ P O H₂C
1’

O H H
H
H

OH OH

UMP Uridine monophosphate Uridylic acid

 NH₂
6
N7
N1 5
8
2 4
3 9

Oˉ N N
O
P O H₂C
Oˉ

O H H
H H

OH H

dAMP Deoxyadenosine mono phosphate

 O

N
HN

Oˉ NH₂ N N
O
P O H₂C
Oˉ 5’ 1’

H H
O H H

OH H

dGMP Deoxyguanosine monophosphate

 NH₂

Oˉ
O N
O
Oˉ P O H₂C
1’

O H H
H
H

OH H

dCMP Deoxycytidine monophosphate

 o

HN CH₃

Oˉ
O N
O
Oˉ P O H₂C
1’

O H H
H
H

OH H

dTMP Deoxy Thymidine monophosphate

 NH₂

N
N

cAMP 9
Adenosine-3’,5’-cyclic N N
mono phosphate 5’ O
O H₂C

H H
H 3’
H

O OH
Oˉ P

O
 NH₂

N
N

9
N N
O
C H₂OH

H H
H 3’ 2’ H
Hydrolysis of RNA
yields Adenosine - O O
2’,3’-cyclic mono P
phosphate O Oˉ
 NH₂

N
N

9
Oˉ Oˉ N N
O
P O H₂C
Oˉ P O
5’ 1’

O O H H
H H

OH OH

ADP Adenosine diphosphate

 NH₂
N
N

9
Oˉ Oˉ Oˉ N N
O
P O H₂C
Oˉ P O P O
5’ 1’

O O O H H
H H

OH OH

ATP Adenosine triphosphate

 A
Oˉ
O
P O H₂C
Oˉ
5’ 1’

O H H
H 3’
H

OH
O

O G
P O H₂C
Oˉ
In nucleic acids, 5’ 1’

nucleotide residues O H H
H H
are joined to each other
by 3’,5’-phosphodiester linkage OH OH