1. Synthetic Analogues of Nucleotides
Lecture # 3
Dr. Shumaila Asim

2. Learning Outcomes Knowledge;
Describe the therapeutic importance of synthetic analogs of nitrogenous bases and nucleosides
Contents
Antiviral drugs
Anticancer drugs
Drugs used for hyperuricemia
Organ transplant drugs
Drugs used for Asthma

3. Synthetic Analogues of Nucleotides
These are also called anti metabolites-therapeutic application
Prepared by altering the ring or sugar moiety.
Used in chemotherapy.

4. Synthetic nucleotide analogs are used in chemotherapy
Chemically synthesized analogs of purines and pyrimidines, their nucleosides and their nucleotides find numerous applications in clinical medicine
Administration of an analog in which either the heterocyclic ring or the sugar moiety has been altered induces toxic effect when the analog is incorporated into specific cellular constituents

5. Their effects reflect one of two processes:
Inhibition by the drug of specific enzymes essential for nucleic acid synthesis
Incorporation of metabolites of the drug into nucleic acids, thus they effect the base pairing required for accurate replication

6. Examples 5-fluoro uracil → thymine analog
5-iodo deoxyuridine → thyminide analog
6-mercaptopurine → purine analaog

7. 6-thioguanine → purine analaog
8-azaguanine → purine analaog
5 or 6-azauridine → pirimidine analaog
6-azacytidine → pirimidine analaog

8. 4-hydroxypyrazolopyrimidine
(allopurinol) → purine analaog
Allopurinol inhibits de novo
purine biosynthesis and
xanthine oxidase activity.
It is used for treatment of
hyperuricemia and gout

9. The nucleoside, cytarabine (arabinosyl cytosine), in which arabinose replaces ribose, is used in chemotherapy and in treatment of viral infections
Azathioprine is catabolized to 6-mercaptopurine and is used during organ transplantation to suppress immunological rejection

10. Use in molecular biology
Nucleic acid analogues are used in molecular biology for several purposes:
As a tool to detect particular sequences
As a tool with resistance to RNA hydrolysis 
As a tool for another purpose, such as sequencing 
Investigation of the mechanisms used by enzyme, such as an enzyme inhibitor
Investigation of possible scenarios of the origin of life
Investigation of the structural features of nucleic acids
Investigation of the possible alternatives to the natural system in synthetic biology