d-Nucleic acids:
Nucleic Acid
1. Chemistry
2. Structure of nucleic acid
3. Nucleotides Purine and pyrimidine bases
4. Nucleoside, Types
5. Biological and Pharmaceutical importance
Chemistry
Introduction
Friedrich Miescher in 1869
• Isolated what he called nuclein from the nuclei of pus cells
• Nuclein was shown to have acidic properties, hence it became called
nucleic acid
• Nucleic acid are polymers that consist of nucleotide residues.
• Located in nuclei of cell
• Hereditary determinants of living organisms
• Elemental composition – carbon, hydrogen, oxygen, nitrogen and
phosphorus
Importance
Among all the properties of living organisms, one is absolutely
important for continuance of life: a living system must be able to
replicate itself.
To do so, an organism must possess a complete description of itself.
In living organisms, this description is stored in the substances called
nucleic acids
Nucleic acid
Nucleic Acid Strands
Nucleic acids are polymers derived from nucleotides. the backbone
consists of repetitive [-phosphate-(deoxy)ribose-] units.
Individual nucleotides are joined by phosphodiester linkages.
Like proteins, nucleic acid chains have a polarity which is defined by
the 5' and 3' ends of the sequence.
By convention, the sequence of bases in a strand is written left-to-
right from the 5' to 3' end
Nucleotides
• Energy rich compounds that drive metabolic process in cell
• Serve as chemical signals, key links in cellular systems that respond
to hormones and other extracellular stimuli
• Structural component of no of enzyme cofactor and metabollic
intermediate
Structure of nucleotide
Each nucleotide is formed by 3 units
– PHOSPHATE,
– SUGAR,
– NITROGENOUS BASE
Nucleotides 6
The deoxyribose, the phosphate and one of the bases
Combine to form a nucleotide
PO4
adenine
deoxyribose
Phosphate
Phosphoric acid
• Molecular formula H3PO4
• Contains 3 monovalent hydroxyl group and a divalent oxygen atom
• All linked to pentavalent phosphorous atom
Sugar
• 5 carbon keto sugar or pentose
• One possess d2 deoxyribose and other contain d ribose
• Both sugar are present in furanose form and beta configuration
• Pentose sugar form esters with phosphoric acid and is called
phosphodiester bond
4
Ribose & deoxyribose
Ribose is a sugar, like glucose, but with only five
carbon atoms in its molecule
Deoxyribose is almost the same but lacks one
oxygen atom
Nitrogenous base
• 2 types of nitrogenous base
• Purine and pyrimidines derivatives
• This base is linked to sugar moiety by same carbon used in sugar-
sugar bond
• PURINS are – Adenine and guanine
• PYRIMIDINE DERIVATIVES are – Uracil,thymine and cytosine
The nucleotides are all orientated in the
same direction
• The phosphate group joins the 3rd
Carbon of one sugar to the 5th Carbon
of the next in line
Adding bases
Their sequence is important
Nucleoside
• When ribose or 2-deoxyribose is combined with purine or
pyrimidine base Nucleoside is formed
Types
Types
Two different types of nucleic acids exist in living organisms, namely
1-Deoxyribonucleic acid or DNA and
2-Ribonucleic acid RNA.
The monomeric unit of DNA is deoxyribonucleotide
while that of RNA is ribonucleotide
The distribution of nucleic acids in the eukaryotic cell
• DNA is found in the nucleus with small amounts in mitochondria
and chloroplasts
• RNA is found throughout the cell
Structure of DNA
Dna is made of two strands of polynucleotide
• The sister strands of the DNA molecule run in opposite directions
(antiparallel) • They are joined by the bases
• Each base is paired with a specific partner: A is always paired with T
G is always paired with C i.e. each Purine is paired with Pyrimidine
• Thus the sister strands are complementary but not identical • The
bases are joined by hydrogen bonds
Purines & Pyrimidines Adenine Cytosine,Guanine Thymine
Levels
•Structure of DNA can be understood in terms of 3 levels of structure
1.Primary structure ; refers to the sequence of its nucleotide residue
2.Secondary structure; it pertains to the helix formed by two DNA
strands
3.Tertiary structure: refers to the 3 dimensional shape. Arises from
supercoiling where double helix is being twisted into compact shape
DNA
The structures and names of the four major deoxyribonucleotides
(deoxyribonucleoside 5’-monophosphates) of DNA.
All nucleotides are shown in their free form at pH 7.0.
The deoxyribonucleotide units of DNA are usually symbolized as A, G, T, and C,
and sometimes as dA, dG, dT, and dC. In their free forms, the
deoxyribonucleotides are commonly abbreviated dAMP, dGMP, cTMP, and
dCMP.
The bases
The most common organic bases are
Adenine (A)
Thymine (T)
Cytosine (C)
Guanine (G)
Joined nucleotides 7
PO4
A molecule of DNA is
formed by millions of
nucleotides joined together
PO4 in a long chain
PO4
PO4
sugar-phosphate + bases
backbone
8
In fact, the DNA usually consists of a double
strand of nucleotides
The sugar-phosphate chains are on the outside
and the strands are held together by chemical
bonds between the bases
2-stranded DNA 9
PO4
PO4
PO4
PO4
PO4 PO4
PO4
PO4
PO4
PO4
PO4
PO4
PO4
PO4
PO4
PO4
10
Bonding
The bases always pair up in the same way
Adenine forms a bond with Thymine
Adenine Thymine
and Cytosine bonds with Guanine
Cytosine Guanine
11
PO4
PO4
adenine thymine
Bonding
PO4
PO4
cytosine guanine
PO4
PO4
PO4
PO4
Pairing up 12
PO4
PO4
PO4
PO4
PO4 PO4
PO4
PO4
PO4
PO4
PO4
PO4
PO4
PO4
PO4
PO4
13
bases
sugar-phosphate The paired strands are
chain coiled into a spiral called
A DOUBLE
HELIX
RNA
• Ribonucleic acid (RNA), like DNA, is a long, unbranched
macromolecule consisting of nucleotides joined by 3′ → 5′
phosphodiester bonds
• The number of ribonucleotides in RNA ranges from as few as 75 to
many thousands
Structure of RNA
• RNA structure is similar to DNA
Similarities: Both are sugar-phosphate polymers and both have
nitrogen-containing bases attached
There are 3 differences between them
• 1) RNA contains a different monosaccharide residue
• 2) RNA contains the bases A, G, C, and U instead of A, G, C, and T
• 3) RNA exists as a single strand instead of a double strand
(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.
b) 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.
• There are intrachain hydrogen bonds between GC and A-U. The
hydrogen bonds are the same as in DNA for G–C while N3 as well as
C4 oxo group of uracil (or dihydrouracil) which pairs with adenine.
(c) 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
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
1. Messenger RNA (m-RNA)
This is the most heterogeneous class of RNA with respect to its size
and stability
They consist of 103 to 104 ribonucleotides.
The m-RNA molecules are formed with the help of DNA template
strand (3’ – 5’) during the process called transcription.
The m-RNA carries a specific sequence of nucleotides in “triplets”
called codons, responsible for the synthesis of a specific protein
molecule.
The 3’–OH end of most m-RNA molecules carries a polymer of
adenylate ribonucleotides consisting of 20 to 250 residues in length.
This is called as “Poly A tail”, the function of which is not yet fully
understood but it seems to maintain the intracellular stability of the
specific m-RNA by preventing the attack of 3' – exonucleases.
the 5' – OH end of the m-RNA carries a cap structure consisting of 7
methylguanosine triphosphate. The cap is probably involved in
recognition of protein biosynthetic machinery and it helps in stabilising
the m-RNA by preventing the attack of 5' – exonucleases. The protein
synthesis begins at 5’ end of the capped structure of m-RNA.
2. 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.
There are at least 20 different t-RNA molecules
3. 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.
Ribosomes contain the third type of RNA known as r-RNA.
The r-RNA forms 80 per cent of the total cellular RNA.
Biological &
Pharmaceutical
importance
DNA is thought of as a blueprint for the body to make proteins.
RNA can catalyze chemical reactions, including joining amino acids
to make proteins.
RNA, in one form or another, touches nearly everything in a cell.
RNA carries out a broad range of functions, from translating genetic
information into the molecular machines and structures of the cell to
regulating the activity of genes during development, cellular
differentiation, and changing environments
Therapeutic Drug Development
Both miRNAs and Si-RNAs represent exciting new potential targets
for therapeutic drug development in humans.
Example:
Cancer
Heart diseases
In disease
If the protein doesn’t work properly, diseases can develop. Some
diseases that occur due to mutations in a single gene include cystic
fibrosis and sickle cell anemia.
Mutations can also lead toTrusted Source the development of cancer.
Changes that occur in at least or more than 1 percent Trusted
Source of the population are called polymorphisms. Examples of
some polymorphisms are hair and eye color.
DNA and its structure have been fundamental in understanding
evolution.
structure and function of DNA has opened up many areas of research,
such as genetic engineering, which is an area of study of increasing
interest. Forensic science and genealogy also rely heavily on DNA
fingerprinting and sequencing for information.
Agriculture
DNA can also be used in agriculture to identify crops as well as in
“cloning of important agronomic trait genes, and molecular marker-
assisted breeding
