chemistry of nucleic acids, history --> Discovered by JOHANN FRIEDRICH MIESCHER central dogma of life components of nucleic acids-->Nitrogenous base +pentose sugar +phosphate group. structure of nucleotides --> purines and pyrimidens minor bases in nucleic acids are 5-methylcytosine,N4-acetylcytosine, N6-methylsdenine, N6,N6-dimethyladenine, pseudouracil. Biologically importanat Bases-->Hypoxanthine, Xanthine, uric acid. Purines bases of plant --> caffeine,theophylline, theobromine

1. CHEMISTRY OF NUCLEIC ACIDS
AND NUCLEOTIDES
By
Dr Shraddha Bharath
PG student
ESIC-MC & PGIMSR
Banglore-10
Department of Biochemistry

2. • Nucleic acids - Bipolymers of nucleotides
• Nucleic acids includes DNA(deoxyribonucleic
acid) and RNA(ribonucleic acids).
• HISTORY : DNA was discovered in 1869 by
JOHANN FRIEDRICH MIESCHER, a Swiss
researcher.

3. • The demonstration that DNA contained genetic
information was first made in 1944 by Avery,
Macleod, and Maccray.

4. • FUNCTIONS OF NUCLEIC ACIDS:
1. DNA  chemical basis of heredity may be regarded as the reserve
bank of genetic information
2. DNA  maintaining the identity of different species of organisms
over millions of years.
3. DNA organised into genes
4. Genes controlprotein synthesis through the mediation of RNA.

5. CENTRAL DOGMA OF LIFE

6. COMPONENTS OF NUCLEIC ACIDS:
• Nucleic acids are polymers of Nucleotides
NUCLEOTIDES :-
1. Nitrogenous base + a pentose sugar + a phosphate group.
2. They perform a wide variety of functions in the living
cells.
3. They also include their role as structural components of
some co-enzymes of B-complex vitamins(Eg: NAD+,
FAD+)
4. Involved  energy reactions of cells
5. In the control of metabolic reactions.

7. STRUCTURE OF NUCLEOTIDES
• Nucleotides : Nucleoside + Phosphate
Nucleobases(Nitrogenous bases)+ sugar + phosphate
Nucleoside = Nitrogenous bases + sugar
Nucleotide = nucleoside + phosphate

8. 1) Nitrogenous bases
- An organic molecule with a Nitrogen atom that
has chemical properties of base.
- Nitogenous bases found in Nucleotide
AROMATIC HETEROCYCLIC
COMPOUNDS
- used in construction of nucleotides.
- Nitrogenous bases
PURINES PYRIMIDINES

9. PURINES PYRIMIDNES
GENERAL FORMULA : C5H4N4 GENERAL FORMULA : C4H4N2
They have 9 membered ring
structure with 4 nitrogens and 5
carbons
They have 6 membered ring with
2 nitrogens and 4 carbons
Consists of a Pyrimidine ring
fused to an imidazole ring
Numbered in anti-clock wise
direction
Numbered in clock wise direction

10. PURINES PYRIMIDNES
Purines are namely :
- ADENINE (A) [6-aminopurine]
- GUANINE (G) [2-amino 6-oxypurine]
Pyrimidines are namely :
-CYTOSINE (C)[2 oxy 4 aminopyrimidine]
-THYMINE(T) [2,4-dioxy-5
methylpyrimidine]
-URACIL(U) [2,4-dioxypyrimidine]
DNA & RNA contain same purines adenine
& guanine
PYRIMIDINE CYTOSINE found in both
DNA & RNA
PYRIMIDINE THYMINE DNA
PYRIMIDINE URACIL  RNA

11. Thymine and Uracil differ in structure by the presence of
Methyl group at 5th position
THYMINE URACIL

12. STRUCTURES OF PURINES
• ADENINE(A)
[6-aminopurine]
• GUANINE(G)
[2-amino,6-oxypurine]

13. STRUCTURE OF PYRIMIDINE
• CYTOSINE(C)
[2-oxy 4-aminopyrimidine]
• THYMINE(T)
[2,4-dioxy 5-methylpyrimidine]

14. URACIL(U) found in RNA
[2,4-dioxypyrimidine]

15. Tautomeric forms of Purines and
Pyrimidines
• The existence of a molecule in a keto(lactam) and
enol(lactim) form is known as tautomerism.
• The heterocyclic rings of Purines and Pyrimidines
with oxo[c=o]functional groups exhibits
tautomerism as:-
• Eg:- tautomeric forms of cytosine

16. • The purine :- Guanine
• The pyrimidine :- Cytosine
Thymine
Uracil
• At physiological pH, the lactam (keto)
tautomeric forms  present
Exhibits
tautomerism

17. Minor Bases found in Nucleic acids are
• These includes : 5-methylcytosine
N4-acetylcytosine
N6-methyladenine
N6,N6-dimethyladenine
Pseudouracil
Function : helps in the recognition of specific
enzymes

18. Structures of minor bases
1] 5-methylcytosine 3] N6- methyladenine
2] N4-acetylcytosine 4] Pseudouracil

19. Other biologically important Bases are
• These are minor Purine bases & present in free
state in the cells.
Hypoxanthine (6-oxypurine)
Xanthine (2,6-dioxypurine)

20. Uric acid(2,6,8-trioxypurine)
Hypoxanthine
Xanthine Intermediates in PURINE BREAKDOWN
Uric acid  end product of PURINE DEGRADATION

21. PURINE BASES OF PLANTS
• These includes:- caffeine of coffee
Theophylline of tea
Theobromine of cocoa

22. 2) SUGARS OF NUCLEIC ACIDS:-
-Sugars are of “FURAN RINGS’’.
-Pentose are found in the nucleic acid structure.
RNA DNA
Contains D-Ribose Contains D-deoxyribose
Ribose has oxygen at 2nd position Deoxyribose has one oxygen less at C2
compared to ribose

23. • Addition of pentose sugar to base produces a
Nucleoside
• If Ribose  ribonucleosides are formed
eg:- Adenosine [ A]
Guanosine [ G]
Cytidine [C]
Uridine [U]
• If Deoxyribose  deoxyribonucleosides are
formed

24. 3) PHOSPHATES:-
Mononucleotide  single phosphate group is
added to a nucleoside.
Eg:- Adenosine Monophosphate(AMP) = adenine +
ribose + phosphate.

25. PRINCIPAL BASES, NUCLEOSIDES AND NUCLEOTIDES

26. The binding of Nucleotide components
• The atoms1] PURINE RING numbered as 1to 9
2] PYRIMIDINE RING  no. as 1 to 6
• The carbons of sugars  Prime(‘) for
differentiation. Thus pentose carbons are 1’ to 5’

27. • In Purine Nucleoside :-
N9 of a Purine ring binds
C1 (1’) pentose sugar
+
Single phosphate group
Nucleoside Monophosphate
• In Pyrimidine Nucleoside :-
N1 of a Pyrimidine ring
C1(1’) pentose sugar
COVALENT BOND Glycosidic linkage

28. i) Nucleoside Monophosphate
• The hydroxyl group of ADENOSINE are esterified
with phosphate group
5’ or 3’ Monophosphates
• Adenosine-5’-monophosphate = AMP
• Adenosine-3’-monophosphate = 3’-AMP
To produce

29. Structure of AMP is

30. ii) Nucleoside di-phosphates
• The esterification/addition of second
phosphate group next to first phosphate to the
nucleoside results in Nucleoside diphosphate.
• Eg:- ADP

31. iii) Nucleoside tri-phosphates
• The esterification/addition of third phosphate
to first & second phosphate to the nucleoside
results in Nucleoside triphosphate.
• Eg:-ATP

32. iv) Cyclic- nucleotides
• A phosphodiester linkage  between  3’ and
5’ position of ribose group  cyclic nucleotides
• Eg:- 3’,5’-cyclic AMP or cAMP : major metabolic
regulator

33. PURINE, PYRIMIDINE AND NUCLEOTIDE
ANALOGS
1. Allopurinol :- Hyperuricemia & Gout
2. 5-Fluorouracil, 6-Mercaptopurine, 8-Azaguanine,
3-deoxyuridine and 5-idouracil :- ANTI-CANCER
These compounds get incorporated into DNA
and blocks the cell proliferation.

34. a. 5-Fluorouracil b. 6-Mercaptopurine:-
c. 8-azaguanine:-c/a 2-amino-6oxy-8-azapurine
2-amino-6-hyroxy-8-azapurine

35. 3. Azathioprine :-
6-mercaptopurine suppress immunological
rejection after transplantation
4. Arabinosyladenine :- neurological disease
c/a 9-b-D-arabinosyl viral encephalitis
degraded

36. 5. Arabinosyl cytosine :- cancer therapy
6. Drugs employed in the treatment of AIDS namely:-
a. Zidovudine/AZT
b. Didanosine
Sugar modified synthetic
Nucleotide analogs

37. STRUCTURE OF DNA
• DNA is a polymer of deoxyribonucleotides or
simply deoxynucleotides
• DNA is composed of 4 deoxyribonucleotides
namely: deoxyadenylate [ dAMP]
deoxyguanylate [ dGMP]
deoxycytidylate [ dCMP]
deoxythymidylate [ dTMP/TMP]

38. Schematic representation of Polynucleotides

39. • Short hand representation:-
P
5’ 3’ 1’
P
5’ 3’ 1’
P
5’ 3’ 1’
P
Horizontal lines : Carbon chain of sugar with base attached to C1’
Near the middle : C3’ phosphate linkage
Other end : C5’ phosphate linkage

40. Chargaff’s rule of DNA composition
• Erwin chargaff in late 1940s
• DNA = Nos. of Adenine and Thymine residues
(A=T)
= Nos. of Guanine and Cytosine residues
(G=C)
Hence, it is known as,
CHARGAFF’S RULE of molar equivalence

41. DNA DOUBLE HELIX
• JAMES WATSON & FRANCIS CRICK IN 1953
(NOBLE PRIZE 1962)
• The DNA is considered as the milestone in the era
of Modern Biology.
• Comparable to a twisted ladder.

42. Salient features
1. Right handed double helix.
Consists of two
Polydeoxyribonucleotide chains,
twisted around each other
2. Two strands antiparallel
3. The width(diameter) 20
A(2nm)
4. Each turn(Pitch)34 A (3.4nm)
with 10 pairs of nucleotides,
each pair placed
3.4A(0.34nm)
5. Hydrophilic deoxyribose
phosphate backbone(3’-5’-
phosphodiester bond) outside

44. 6. Complementary to each other due to base pairing
7. Two strandshydrogen bonds formed by
complementary basepairs
8. The hydrogen bonds are formed between purines and
pyrimidine.

45. 9. CHARGAFFS” RULE
10. The genetic information residues on one of
the two strandstemplate strand/sense strand,
the oppositeanti-sense strand.

46. Conformations of DNA double helix
• The double helix structure of DNA exists  6
different forms A-E & Z. B, A & Z are important.
• B-form  WATSON & CRICK
• It is believed that transition between different helical
forms of DNA plays a significant role in regulating
gene expression.

47. Comparision of structural features of different
conformations of DNA double helix

48. Other types of DNA structure
• These structures are important for molecular
recognition of DNA by proteins and enzymes
Bent DNA
Kinked DNA
Triple stranded DNA
Four stranded DNA

49. Bent DNA & Kinked DNA
• Bent conformation  when
Adenosine tracts are replaced by
other bases.
• Bending of DNA strucure due
to:
Photochemical damage or
mispairing of bases
 Certain antitumours drugs like
[CISPLASTIN]

50. Triple stranded DNA
• Due to additional hydrogen bonds
• Thus, thymine can selectively
form two ‘’HOOGSTEEN-
HYDROGEN BONDS”TO THE
ADENINE OF A=T pair to form
T-A-T
• C-G-C
• Also called as HOOGSTEEN-
TRIPLE HELIX.
• Due to negatively charged
backbone strands in triple helix ,
an increased electrostatic
repulsion

51. Four stranded DNA
• Polynucleotides with high contents of GUANINE
forms tetrameric structure ‘’G-Quartets”
• These structures are planar and are connected by
Hoogsteen-hydrogen bonds.
• Antiparallel four stranded DNA structure
‘’G-tetraplexes’’ as the ends of eukaryotic
chromosomes namely telomers 
GUANINE

53. • In recent years,
Telomeres  targets for anticancer
chemotherapies.
• G-tetraplexes :
1. Implicated in the recombination of
immunoglobulin genes
2. In dimerization of double-stranded genomic RNA
of the Human Immunodeficiency Virus [HIV].

54. The size of DNA molecule-units of length
• On an average B-DNA :- Thickness  0.34nm
Mol. Weight 660 daltons
• Measurement of length :- DNA double helix is
considered & expressed in the form of
basepairs(bp).
1kb=103 bp
1mb=106bp
1gb=109bp

55. • Length of the DNA varies from species to species
& expressed in terms of
Base pair (bp) contour length
composition
reprsents total
length of the genomic
DNA in a cell
Eg:- diploid human cell(46 chromosomes) 6x109 bp &
counter length 2m

56. Denaturation of DNA strands
• Two strands of DNA helix
 hydrogen bonds
Separation of polynucleotide
strands
• The phenomenon of loss of
helical structure of DNA is
known as Denaturation
• The phosphodiester
bondsnot broken • RENATURATION:
separated DNA strands
forms back double helix
Disruption of these
hydrogen bonds

57. • Melting temperature(Tm) :at which half of the
helical structure of DNA is lost.
• Higher the bond greater the temperature required to
break. Hence, G=C > A=T

58. Organization of DNA in the cell
Organization of organization of
prokaryotic DNA eukaryotic DNA
associated with various
proteins to for chromatin
gets organized into
compact structure
namely chromosomes

59. DNA double helix is wrapped around the
core proteins namely HISTONES

60. Organization of Eukaryotic DNA in the cell

61. STRUCTURE OF RNA
• RNA is a polymer of ribonucleotides held
together by 3’,5’-phosphodiester bridges.
RNA DNA
STRAND Single stranded Double stranded
SUGAR Ribose sugar Deoxyribose sugar
NITROGENOUSE
BASES
Adenine , Guanine, Cytosine
& Uracil
Adenine, Guanine,
Cytosine & Thymine
ADENINE pairs with uracil Pairs with thymine

62. Conti…….
RNA DNA
CHARGAFF’S RULE Do not obeys.Purine pyrimidine Obeys. Purine pyrimidine
GENETIC
MATERIAL LENGTH
RNA is genetic material in some
viruses. Short and consisting few
thousands of nucleotides
Genetic material in all living
organisms. Quite large
consisting of millions of
nucleotides
TYPES mRNA, rRNA, tRNA Only in one form
SITES mRNA  nucleolus
rRNA & tRNA  cytoplasm
Nucleus , nucleolus and
extrachromosomal DNA in
mitochondria and chloroplast

63. RNA DNA
SUSCEPTIBILITY TO
ALKALI HYDROLYSIS
Alkali can hydrolysis RNA Cannot be subjected to
hydrolysis
ORCINOL COLOUR
REACTION
Histologically identified by
orcinol colour due to
presence of Ribose
No orcinol colour reaction

64. Types of RNA
• 3 major types of RNA are :-
1] Messenger RNA(mRNA) :- 5-10%
2] Transfer RNA (tRNA) :- 10-20%
3] Ribosomal RNA (rRNA) :- 50-80%

65. Types of RNA

66. Messenger RNA(mRNA)
• Has high molecular weight with short half life.
• Synthesized  nucleus(in eukaryotes) as
heterogeneous nuclear RNA(hnRNA).
• Acts messenger, transporting the
information from the gene in DNA to
synthesize proteins.

67. DNA (template strand)
hnRNA
Functional mRNA
Cytoplasm
Protein synthesis
RNA polymerases
liberates
enters
To pariticipate

68. 1. Prevent the hydrolysis
of mRNA by 5’-
exonucleases
2. Recognition of mRNA
for protein synthesis
1. Stability to mRNA
2. Prevents it from the
attack of 3’-exonucleases

69. Transfer RNA(tRNA)/soluble RNA molecule
• 71-80 nucleotides.
• Mol. Wt :- 25,000
• Structure of tRNA [for alanine] was first
elucidated by HOLLEY.
• Atleast 20species of tRNAs, corresponding to
20 amino acids present in protein structure.
• They transfer AAs from cytoplasm to the
ribosome for protein synthesis.

70. Structure of tRNA
• Resembles clover leaf.
• Has 4 arms, each arm
with a base paired
stem.
• 4 arms are :-
1] Acceptor arm
2] Anticodon arm
3] DHU arm
4] Pseudouridine arm
5] Variable arm

71. 1] ACCEPTOR ARM :-
Capped with a sequence CCA(5’ to 3’)
The amino acid is attached to this arm
7 base pairs
3’ end hydroxyl group is forming an ester
bond with the carboxyl end of amino acids.

72. 2] The anticodon arm:-
 it recognizes the triplet nucleotide codon
present in mRNA
 codon and anticodon are complementary
to each other.
Eg:- mRNA has a codon  sequence UUU,
anticodon sequence of the tRNA AAA.
 the tRNA act as adapter molecules
between mRNA and the amino acids
coded by it.

74. 3] D-arm/ DHU arm:-

75. 4] TyC (Pseudouridine) arm

76. 5] Variable arm:-

77. • BASE PAIRS IN tRNA
The acceptor arm :- 7bp
Anticodon arm :- 5bp
TYC arm :- 5bp
D arm :- 4bp

78. Ribosomal RNA (rRNA)
• Factories of protein synthesis.
• The eukaryotic ribosomes are composed of
two major nucleoprotein complex
60s units 40s units
28s rRNA, 5s rRNA and 18s rRNA
5.8s rRNA

79. Catalytic RNAs - Ribozymes
• The RNA component of a
ribonucleoprotein is catalytically active,
such RNAs are termed as ribozymes.
• RNAase P(ribonuclease P)  is a ribozymes
containing protein and RNA component.
• RNAase P
Cleaves tRNA precursors generate mature
tRNA molecules.

80. • Recombinant Ribozymes (rRibozymes) :
these ribozymes are used as therapeautic
agents to cure disease.

82. Catalytic RNAs - Ribozymes
RIBOZYMES(s) BIOCHEMICAL REACTION(s)
rRNA Peptide bond formation in protein
biosynthesis
Rnase P RNA cleavage & ligation
Self-splicing RNAs DNA cleavage
RNAs of splicesomes RNA splicing
In vitro selected RNAs RNA polymerization
RNA phosphorylation
RNA aminoacylation
Glyscoide bond formation
Oxidation-reduction reactions disulfide
exchange

83. • RNA molecules  adapt tertiary structure of
protein (ie., enzymes)
• But, the specific conformation of RNA 
function as biocatalyst.
• It was first believed that ribozymes(RNAs)
 functioning as catalyst before the
occurrence of protein enzymes.