CHEMISTRY OF NUCLEIC

ACIDS

By
Dr Aminu Ishaka
MBBS (UDUS, Nigeria), MMDSC (IIUM, Malaysia), PhD (UPM,
Malaysia
06/22/2024 Dr Aminu 1
 Learning objectives

To know
• nucleic acids and types of nucleic acids
• The structure and components of DNA & RNA
• The base composition of DNA & RNA
• Conformation of DNA
• Functions of DNA & RNAs

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 Introduction

• Friedrich Miescher in 1869 isolated what he

called nuclein from pus cells
• The nuclein was later found to be acidic in
properties and was called nucleic acid
• In 1944, Avery, Macleod and MacCarty demonstrated that DNA contains
genetic information

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 Introduction
• Nucleic acids are 3rd class of biomolecules or
biopolymers which are essential for life
• Have high molecular weight
• Two major classes of nucleic acids
• Deoxyribonucleic acid (DNA): carrier of genetic
information, found in nucleus, mitochondrium
& chloroplast
• Ribonucleic acid (RNA): an intermediate in the
expression of genetic information and other
diverse roles found throughout the cell

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 Building blocks of nucleic acids
• Nucleic acids are made up of units of a nucleotide
• Nucleotides are made up of three structural
subunits
1. Sugar: ribose in RNA, deoxyribose in DNA
2. Heterocyclic (nitrogen) base: sequence of
bases on DNA form the genetic code
(1 + 2 = nucleoside)
3. Phosphate

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 phosphate

sugar base

3
phosphate phosphate
1 2
sugar base 2
sugar base sugar base
nucleoside
1
phosphate
nucleotide

sugar base

nucleic acid

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Sugar of nucleic acids-pentose

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 Heterocyclic (nitrogenous) bases
• Purines:adenine (A) and guanine (G)
• Pyrimidines: cytosine (C), thymine (T) and uracil (U)

4-amino-2-oxypyrimidne

06/22/2024 6-aminopurine
Dr Aminu 8
 Tautomeric form of purines
and pyrimidines
• Tautomerism is existence of a molecule in a keto
(lactam) and enol (lactim)
• Heterocyclic rings of purines and pyrimidines also occur
as such

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 Tautomeric form of purines and
pyrimidines

Lactim Lactam
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 Minor bases
• Several unusual bases occur in DNA and RNA
• 5-methylcyclotosine
• N4-acetylcytosine
• N6-methyladenine
• N6,N6-dimethyladenine
• Pseudouracil
• Other biologically important bases are
• Hypoxanthine (6-oxopurine)
• Xanthine (2,6-dioxopurine) & Xanthine
alkaloids:Theophyllin, theobromine and caffeine
• Uric acid (2,6,8-trioxopurine)

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 Nucleosides vs nucleotides

Adenosine (nucleoside)
Nucleotide starts here
Are phosphoric acid esters of nucleosides

• Long chain nucleotide

= polynucleotide
• Short chain =
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oligonucleotide 12
Bases, nucleosides & nucleotides in RNA
and DNA

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Complementarity rule for base
pairing
• Adenine always base pairs with Thymine (or Uracil if
RNA) A-T or A-U
• Cytosine always base pairs with Guanine C-G

• This is because there is only exactly enough room for

one purine and one pyrimidine base between the two
polynucleotide strands of DNA/RNA

• These bases are said to be complimentary to each

other

06/22/2024 GKM/MSB100/LECT 02/2013

Complementary base pairs

A-T Base pairing G-C Base Pairing

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 Adenosine derivatives
• The most common is 3’-5’-cyclic adenosine
monophosphate-cAMP. Formation is catalyzed by
adenylate cyclase
• cAMP is a powerful second messenger in signal
transduction events eg protein kinase cAMP-
dependent pathway of glucagon hormone
• cAMP also regulates ion channel by interaction with
the channel’s proteins
• S-adenosylmethionine: a form of activated methionine
which serves as a methyl donor in methylation
reactions

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Guanosine derivatives
• Cyclic guanosine monophosphate cGMP is also a
second messenger. Antagonizes the effect of cAMP.
Formation catalyzed by guanylate cyclase
• Most important cGMP coupled signal transduction
is in photoreception

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 Primary structure of nucleic acids
• The primary structure of a nucleic acid is the nucleotide sequence
• The nucleotides in nucleic acids are joined by phosphodiester
bonds (Covalent bond)
• The 3’-OH group of the sugar in one nucleotide forms an ester
bond to the phosphate group on the 5’-carbon of the sugar of the
next nucleotide

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Reading primary structure of nucleic
acids
• A nucleotide polymer
(nucleic acid) has a free 5’-
phosphate group at one
end and a free 3’-OH group
at the other end
• The sequence is read from
the free 5’-end using the
letters of the bases
• This example reads
5’—A—T—G—3’ for DNA
5’—U—G—C—3’ for RNA
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Secondary structure of nucleic acids
•Secondary structure is the local folding
of the polynucleotide chain (s) to form
helix
• Here bonding is non-covalent

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 Polymer of deoxyribonucleotides-DNA
• In DNA there are two strands of nucleotides that wind together
in a double helix (twisted ladder shape)
• the strands run in opposite directions
• the bases are arranged in step-like pairs
• the base pairs are held together by hydrogen bonding
• The pairing of the bases from the two strands is very specific, the
strands are identical but complimentary due to base pairing
• The complimentary base pairs are A-T and G-C
• 2 hydrogen bonds formed between A and T
• 3 hydrogen bonds formed between G and C
• Each pair consists of a purine and a pyrimidine, so they are the
same width, keeping the two strands at equal distances from
each other
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 Base pairing in DNA double helixc

3.4 A0

]Minor groove
Hydrophilic 10 base bases per turn

34 A0
] Major groove
Turn contains 10 bases

20 A0

06/22/2024 Watson & Crick Dr

model,
Aminu 1953 22
 DNA molecule
• Erwin Chargaff in late 1940 quantitatively analyzed DNA
from different species and observed that the number of
purines and pyrimidines are equal on DNA
• A=T and G=C : Chargaff’s rule of molecular equivalence
of purines and pyrimidines in DNA
• The strength of the DNA double helical structure is due
to this molar equivalence
• Single-stranded DNA & RNA do not obey the Chargaff’s
rule; so also double-stranded RNA
• The strands of DNA are said to be antiparallel-one goes 5’
to 3’ direction while the other 3’ to 5’ direction
• H bonds only occur between purines and pyrimidines
• The strand that carries genetic information is called
template strand
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The central dogma of molecular biology

• Replication-DNA making a copy of itself. Making a

replica
• Transcription-DNA being made into RNA. Still in
nucleotide language
• Translation-RNA being made into protein. Change to
amino acid language
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 Replication
• Remember that DNA is self complementary
• Replication is semiconservative
• One strand goes to next generation
• The other is new
• Each strand is a template for the other
• If one strand is 5’ AGCT 3’
• The other will be: 3’ TCGA 5’
• Exercise: what is the complimentary strand of
3’ ACTAGCCTAAGTCG 5’
• Answer of the exercise
5’ TGATCGGATTCAGC 3’
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Differences between replication
and transcription
Replication Transcription

template double strands single strand

dNTP
substrate (deoxyribonucleoside NTP
-5’-triphosphate)
primer yes no

Enzyme DNA polymerase RNA polymerase

dsDNA (double
product ssRNA
stranded DNA)
base pair A-T, G-C A-U, G-C
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Similarities between replication
and transcription
• Both processes use DNA as the template.
• Phosphodiester bonds are formed in both cases.
• Both processes directions are from 5´ to 3´.

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Conformation of DNA
• The conformation of DNA
nucleotides varies giving
rise to DNA forms or variants
• At least 6 different forms
exist: A to E and Z.
• However, A, B and Z are the
most important
• B form is the most
predominant under
physiological condition

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Unusual DNA forms
• Bent DNA: when adenine base is replaced by another
base. Adenine confers rigidity to DNA
• Other causes of bending are mis-pairing ,
anticancer drugs (e.g cisplatin) and photochemical
damage to DNA
• Triple-stranded DNA: occurs due to additional H
bonds between bases. Thymine forms 2 Hoogsteen H
bonds with adenine to form T-A-T or cytocine with
guanine C-G-C to give triple Hoogsteen helix
• The triple-helix DNA is less stable compared to
double-helix

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Unusual DNA forms
• Four-stranded DNA: high content of guanine gives
a tetrameric strucure called G-quartetFour-
stranded DNA called G-tetraplex

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 DNA storage
• In eukaryotic cells (animals, plants,
fungi) DNA is stored in the nucleus,
which is separated from the rest of
the cell by a semi-permeable
membrane
• Amazingly, 2 meter long DNA is packed in 10
micrometer wide nucleus
• The DNA is only organized into
chromosomes during cell division
• Between replications, the DNA is
stored in a compact ball called
chromatin (a little less than 2 turns),
and is wrapped around a set of 8
proteins called histones to form
nucleosomes
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DNA denaturation
• This is the loss of helical
structure of DNA usually by
disruption of H bonds which
hold the helix
• N.B phosphodiester bond is
not affected by denaturation
• Change in pH and increase in
temperature usually cause
DNA denaturation
• Decrease dielectric constant
by alcohols & ketones,
exposure to amides or urea

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 RNA
• Much more abundant than DNA
• Single stranded structure
• Contains ribose (DNA 2’-deoxy
ribose)
• Contains uracil base
• Does not obey Chargaff’s rule
• Sueceptible to alkaline hydrolysis
• Retains all information of DNA
• Specific RNA for specific functions
• Structure similar to A-form DNA
• 3 major types
• mRNA : 5-10%
• tRNA: 10-20 %
• rRNA: 50-80 %
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Important functions of RNA
• mRNA directs ribosomal synthesis of
polypeptides known as translation
• Also serve structural function by its 1/3 portion
being protein
• Especially in viruses serve as genetic
information carrier

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Types of RNA & their functions

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