Download 3)Synthetic Analogues of Nucleotides

Synthetic Analogues of Nucleotides
Lecture # 3
Dr. Shumaila Asim
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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
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Synthetic Analogues of Nucleotides
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These are also called anti metabolites-therapeutic
application
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Prepared by altering the ring or sugar moiety.
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Used in chemotherapy.
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Synthetic nucleotide analogs are used in chemotherapy
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Chemically synthesized analogs of purines and
pyrimidines, their nucleosides and their nucleotides find
numerous applications in clinical medicine
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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
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Their effects reflect one of two processes:
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Inhibition by the drug of specific enzymes essential for
nucleic acid synthesis
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Incorporation of metabolites of the drug into nucleic acids,
thus they effect the base pairing required for accurate
replication
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Examples
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5-fluoro uracil → thymine analog
5-iodo deoxyuridine → thyminide analog
6-mercaptopurine → purine analaog
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6-thioguanine → purine analaog
8-azaguanine → purine analaog
5 or 6-azauridine → pirimidine analaog
6-azacytidine → pirimidine analaog
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4-hydroxypyrazolopyrimidine
(allopurinol) → purine analaog
Allopurinol inhibits de novo
purine biosynthesis and
xanthine oxidase activity.
It is used for treatment of
hyperuricemia and gout
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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
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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
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