By Dr Lee YH

Heterocycles & Nucleic Acids

By Dr Lee YH

Contents
What are heterocyclic compounds? Aromaticity & reactions of heterocycles Purines & pyrimidines Nucleosides, nucleotides & nucleic acids The structure of DNA Replication & synthesis of DNA Protein synthesis by DNA. DNA sequencing Polymerase chain reaction (PCR)
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Heterocyclic Compounds
The heterocyclic ring consists of N, O or S atoms apart from C. Examples: cyclic ether (epoxide, tetrahydrofuran), cyclic esther (lactone), cyclic amides (lactam) & cyclic aromatic amines (pyridine). Chemical properties similar to the noncyclic compounds.
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Examples of Heterocyclic Compounds

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Electrophilic Substitution of Pyrrole

Demonstrate aromaticity similar to benzene

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Electrophilic Substitution of Pyridine

A difficult reaction occurs slowly. Electron withdrawing by ring N atom reduces the electron density.

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Nucleophilic Substitution of Pyridine

Easier to occur compared with electrophilic reaction.

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Examples of Heterocyclic Aromatic Compounds

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Uses of Heterocyclic Compounds

Antibiotic Sedative drugs Sweet flavouring

Malaria drug

Hallucinating drug

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Purine & Pyrimidine Compounds

They exist in nucleic acids

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Nucleoside
Nucleoside is a combination of a sugar and heterocyclic amine. Two major components: - Heterocyclic amine bases (purine and pyrimidine) - Monosaccharides (5 carbon, furanose) : D-ribose or 2-deoxy-D-ribose. Heterocyclic base attached to ribose or deoxyribose via the N-glycosidic bond at C1 ( bond).
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Nucleosides
Nucleoside from DNA consists of 2deoxy-D-ribose sugar and one of the four amine bases. Amine bases: adenine (A), Guanine (G), Cytosine (C) dan Thymine (T). Nucleoside from RNA contained Dribose sugar and adenine, guanine, cytosine dan uracil (U).
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Examples of nucleosides

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Examples of nucleosides

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Nucleotides
Each nucleotide contains 3 parts: Heterocyclic base (purine or pyrimidine) - Monosaccharides (5 carbon, furanose) : D-ribose or 2-deoxy-D-ribose. Phosphate ion. Phosphate is in the form of esther and attached to positions C5 or C3
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The General Structure of Nucleotides

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Examples of Deoxyribonucleotide

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Examples of Ribonucleotide

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Nucleic Acids
Nucleic acids: Nucleic acid is a polymer made of small nucleotides. Deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) keeps hereditary information (genetic information). By transcripting and translating this information, they control cell growth & division, protein biosynthesis (e.g. enzymes) in cells.
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Building Up the Structure of Nucleic Acid

Nucleic acid

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Examples of Nucleic Acid Structure

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The Basic Structure of DNA

Bonds that connect all units of DNA are phosphate esther bonds. Connection occurs between a phosphate esther bond and the 3-OH of ribose. A straight backbone containing sugar units and phosphate. The sequence of bases attached to the backbone carry the genetic information.
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A Comparison Between Protein & Nucleic Acids.

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The Secondary Structures of DNA

Click & Watson Model This structure enables the understanding of genetic information: - Conservation of genetic information - How does it transfer during cell division. - How does it transcript for the synthesis of protein. The ratio of purine:pyrimidine = 1:1 The ratio of A:T=1:1 dan G:C = 1:1
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DNA Composition of Some Species of Living Organisms

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The 3-D Structure of Nucleic Acid

Double helix structure with the backbone outside and the base pair inside.

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The Helix Structure of DNA

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Human DNA
The nucleus of a human cell contains 46 chromosomes (23 pairs). Each chromosome is made up of thousands of DNA fragments (genes). All the genes in human made up the human genome. Each DNA chain has length of 12 cm with and has 250 millions base pair.
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Replication of DNA
The replication process is the production of copies of DNA similar to the original one. The information kept in the DNA does not change during copying.

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Replication of DNA

DNA polymerase enzymes Add bases DNA ligase enzymes connect the broken strands

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Laboratory Synthesis of DNA

Protect O-P:

Protect 3 OH: catalyst

Continued
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Laboratory Synthesis of DNA

Oxidation to form the phosphate group

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Transcription of DNA Information & Protein Synthesis

Transcription Information in DNA is read and transfer out of the nucleus to ribosome for protein synthesis. Messenger RNA(mRNA) Carry the genetic information to the ribosome. Ribosome RNA (rRNA) Form the content of a ribosome with proteins. Transfer RNA (tRNA) Transfer amino acids to ribosome to form proteins.

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Codon Code in mRNA that enables the uptake of types of amino acids to form proteins. Examples : AUG Met GUA Lys UUU - Val

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Biosynthesis of Proteins

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Biosynthesis of Proteins

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Determination of DNA Base Sequence

The sequence of bases in DNA is determined by cutting or cleaving the DNA into smaller fragments. The nucleotide sequence of each fragment is determined. Restriction endonuclease enzymes are used to cleave the DNA.

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Determination of DNA Base Sequence

Each fragment is marked by reacting chemically with radioactive phosphate. The DNA helix is also opened and separated. All fragments with various bases can be separated by gel electrophoresis. The radiation from the separated products darkens a photographic plate, which used as a detection method 38 (autoradiography).

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Determination of DNA Sequence

The movement of fragments on the gel layer depends on the size and charge of the DNA fragments.

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Fragment AG

Fragment G

Fragment C

Fragment CT

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Polymerase Chain Reaction

Important in multiplying the quantity of certain DNA sequence. From a single DNA molecule, it can produce 100 billion copies of the same DNA. Useful for the determination of DNA in the field of: - Molecular biology - Medicine (diagnosis of genetic diseases, AIDS virus, carcinomas, hepatitis) - Forensic chemistry.
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Polymerase Chain Reaction (PCR) Utilize the properties of the polymerase enzymes that can combine nucleotides to form oligonucleotides starting at the end position-3. The oligonucleotides involved are called primers. Primer will be attached to a complementary DNA strand or template.
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Polymerase Chain Reaction (PCR)

In the presence of nucleotide triphosphate, the enzyme will add nucleotides to the primer according to the sequence in the template. The process will continue until it reaches the end position-5 of the template. It is not necessary to know the actual sequence of the original DNA before the process.
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Polymerase Chain Reaction (PCR)

The dublex DNA (double strand) needs to be open up by heating to form the template before the primer is attached (annealed) at its end. The addition of enzyme and nucleotides will initiate the PCR process. Each cycle will increase the amount of DNA by two folds. 10 cycles = 1000 times DNA, 20 cycles = 1 million times DNA.
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Polymerase Chain Reaction (PCR)

Steps involved in PCR

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Polymerase Chain Reaction (PCR)

Production of DNA by cycles

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