Nucleic acids
By
Dr. N C Baruah
The chemical basis of life is the Deoxyribonucleic acid; in short, the DNA.
• Living organisms pass all the characteristics to the next generation; means they have the ability to form
replica, or they replicate.
• To replicate, the living organisms must store all the descriptions of their life in one component. This
component is nothing but the Nucleic acid; the Deoxyribonucleic acid (DNA).
• DNA controls heredity and controls all the functions of a living organism.
• Chemically DNA is a polymer of nucleotides ( ~1010 Nucleotides)
• Nucleotides are joined by 3’-5’ phosphodiester bonds and form a long chain.
• A Nucleotide is a phosphated Nucleoside. Only monophosphates form the DNA.
• A nucleoside is a condensed nitrogenous base with a 2-deoxyribose sugar.
• The 2-deoxyribose is a pentose sugar. The nitrogenous bases are either pyrimidine or a purine.
• So a nucleotide is composed of a nitrogenous base(pyrimidine or a purine), linked to a deoxyribose by
glycosidic bond and a phosphate group on the sugar at 5’ position.
The DNA has two Pyrimidine & two Purine bases
• Pyrimidine bases: the Cytosine and Thymine.
Cytosine Thymine
• Two purine bases: the Adenine and Guanine
Adenine (6-aminopurine) Guanine (2amino-6-oxopurine)
Nucleosides are formed by combining a deoxyribose to the pyrimidine or
the purine bases
• The nucleoside of a DNA is formed by combination of 2-deoxy-D-ribose through its 1st
carbon to the 1st Nitrogen of pyrimidine or the 9th Nitrogen of purine by a beta N-
glycosidic linkage. The nucleosides so formed are d-cytidine, d-thymidine, d-adenosine
and d-guanosine.
• Cytosine + 2-deoxy-D-ribose =d-Cytidine
• Thymine + 2-deoxy-D-ribose =d-Thymidine
• Adenine + 2-deoxy-D-ribose = d-Adenosine
• Guanosine + 2-deoxy-D-ribose = d-Guanosine
The nucleoside is formed by combining a nitrogenous base with the sugar
deoxyribose.
2-Deoxyribose
Cytidine = deoxyribose + cytosine Thymidine =deoxyribose + thymine
Adenosine = deoxyribose + adenine Guanosine =deoxyribose + guanine
Nucleotides are formed by combining a phosphate group to the
nucleoside at 5’ carbon of deoxyribose
• The Nucleotides are 5’-monophosphates of the nucleosides.
• d-Cytidine + Pi = Cytidine-5’-monophosphate (d-CMP), (d-Cytidylic acid)
• d-Thymidine + Pi = Thymidine-5’-monophosphate (d-TMP), (d-thymidylic acid)
• d-Adenosine + Pi = Adenosine-5’-monophosphate (d-AMP), (d-Adenylic acid)
• d-Guanosine + Pi = Guanosine-5’-monophosphate (d-GMP), (d-Guanylic acid)
The nucleotide is formed by combining a phosphate group to the 5th carbon of
deoxyribose of the Nucleoside
d-cytidine-5’-monophosphate d-thymidine-5’-monophosphate
d-adenosine-5’-monophosphate d-guanosine-5’-monophosphate
Structure of DNA
• Two deoxyribonucleotides are bonded (Joined) together by phosphodiester linkage
between the 3’-hydroxyl group and 5’-phosphate group, that continues to form a linear
polymer or a primary DNA strand.
• The numbers and sequence of purine and pyrimidine nucleotides denote the primary
structure.
• In this way one after another nucleotide joins to form a polynucleotide.
• The end of the polymer that has a phosphate group is the 5’ end, while the end having
free hydroxyl group is the 3’ end.
• The bases in the linear polymer are held laterally outside.
• Two polymeric chains of deoxyribonucleotides are held together in opposite (antiparallel)
direction side by side by forming hydrogen bonding between the atoms or groups of the
bases, which is known as double stranded DNA or double helix secondary DNA.
• This double stranded helix is known as secondary structure of DNA.
• The double stranded helix structure was first proposed by James Watson & Francis Crick
in 1953; and they were awarded Nobel Prize in 1962.
Phosphodiester linkage in DNA
5’-end
Negative charges
adenine
Phosphodiester
linkage guanine
cytosine
3’-end
Double helix of DNA :Watson & Crick model satisfy the Chargaff’s molar
equivalence rule; i.e A=T & G=C or Purine = pyrimidine
3’-end
5’-end adenine
thymine
cytosine
guanine
adenine
5’-end
thymine
Hydrogen bond
3’-end
DNA structures
• Two polymeric chains of deoxyribonucleotides are held together in opposite
(antiparallel) direction side by side by forming hydrogen bonding between the atoms or
groups of the bases, which is known as double stranded DNA or double helix secondary
DNA.
• The adenine and thymine form two hydrogen bonds, while Guanine and cytosine forms
three hydrogen bond in between. The bonding between Guanine and cytosine is about
50% stronger than the bonding between adenine and thymine.
• The 3’-5’ strand is the coding strand or the template strand or the sense strand and the
5’-3’ strand is the antisense strand.
• The two strands remain in twisted around a central axis.
• There are six different forms (conformations) of DNA: these are A, B , C, D, E and Z. Out
of these B, A and Z are most common forms.
• The B and A forms are right handed helix, while Z form is a left handed helix.
DNA structures
• In one turn (3600) of the helix measures 34A0 (3.4nm). The B-DNA has 10 base
pairs (10bp), the A-DNA has 11 bp and Z DNA has 12bp that runs in a zig-zag
fashion.
• There may be other forms of DNA, the bent DNA, triple stranded DNA, four
stranded DNA. These unusual structures are for molecular recognition by proteins
and enzymes.
• The triple stranded DNA occurs when two additional hydrogen bonds (Hoogsteen
hydrogen bond) forms between thymine and adenine (T-A-T) and cytosine and
guanine (C-G-C).
• Similarly four stranded G-quartet (parallel) and G-Tetraplex(antiparallel) DNA
structures are also found when guanosine base is higher.
• While coiling the double stranded DNA forms some major and some minor
groves.
• These groves help the protein, histones to fit in the coiling.
RNA: Ribonucleic acid is a polymer of ribonucleotides.
• The Ribonucleic acid, RNA, has ribose sugar. Uracil
• The pyrimidine base thymine is not found in RNA, which is substituted by uridine.
• The RNA is a single stranded nucleic acid.
• The Chargaff’s molar equivalence rule is not satisfied by RNA bases.
• There are three major types of RNAs are found , these are messenger RNA, transfer RNA
and ribosomal RNA.
• The main function of messenger RNA(m-RNA) is synthesis of protein. It carries all codes
for protein synthesis from DNA and it transfers the codes through the transfer RNA (t-
RNA).
• The transfer RNA(t-RNA) has a five armed structure: consisting of the acceptor arm, the
anticodon arm, the D-arm, and the TΨC arm, and a variable arm.
RNA
• The acceptor arm is capped with CCA coding sequence. The incoming amino acid
binds at this site.
• The anticodon arm has three specific base sequences (anticodon)for recognition of
codes from messenger RNA and accordingly an amino acid is attached to the
acceptor arm.
• The D-arm has dihydrouridine base.
• The TΨC arm has thymine, pseudouridine and cytosine.
• The variable arm has changing base pairs.
• The main function of transfer RNA is synthesis of protein.
• The Ribosomal RNA (rRNA) is the main factory for synthesis of proteins.
•
Other bases found in the nucleic acids in minor amounts:
• 5-methylcytosine, N4-acetylcytosine, N6-methyladenine, N6,N6-dimethyladenine, and
pseudouracil. These bases help in recognition of specific enzymes.
• Biologically important bases are found in the cells as free bases.
• They are either intermediates in purine synthesis or their degradation product.
• The main of such bases are hypoxanthine and xanthine, which are the intermediates of purine
synthesis.
• The uric acid is the metabolic product of purine bases.
• Some methylated analogs of purine bases are found in plants, which are pharmacologically
important.
• The common such compounds are Caffeine, theophylline and theobromine.
Hypoxanthine Allopurinol Xanthine Uric acid
The true nucleic acid bases are Adenine, Guanine, Cytosine, Thymine and
Uracil; there analogs cannot form the right nucleic acids.
The analogs replaces the true bases and by incorporation in the nucleotide
formation ultimately results a false nucleic acid. So cell multiplication stops ,
therefore these analogs are used a s a anti-cancer drugs.
6-Mercaptopurine 5-Fluorouracil 8-Azaguanine
The nucleic acid analogs
Medicinally important purine and pyrimidine analogs
• Some of the purine and pyrimidine analogs or the analogs of nucleoside and
nucleotides are useful in the treatment of diseases.
• Allopurinol is an analog of hypoxanthine, which is a competitive inhibitor of
xanthine oxidase, so decrease production of uric acid and hence used for
treatment of gout and hyperuricemia.
• Azathioprine is used in suppression of immunological reaction in the process of
transplantation.
• 5-Fluorouracil, 3-deoxyuridine, 6-azauridine, 6-azacytidine etc are beneficial in the
treatment of neoplastic diseases because they are thymidylate synthase inhibitor.
• 6-mercaptopurine, 8-azaguanine are incorporated in the DNA and incorporation of
such compounds in DNA lead to false coding or non-coding and cell multiplication
stops.
• Arabinosyladenine is used in neurological disorders and arabinosylcytosine is used
in cancer treatment.
References
• Biochemistry 4th edition, Satyanarayana & Chakrapani
