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Antibiotics as nucleoside analouges
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Nucleoside antibiotics are structural analouges for physiologically important purine and pyrimidines nucleosides.
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Inhibition of denovo synthesis of purines
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Inhibition of interconversion of nucleotides
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Inhibition of utilization of nucleotides due to incorporation of nucleoside analouges antibiotics into polynucleotide.
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Exsamples Formycin A is a nucleoside analouge for adenosine that inhibits: Purine biosynthesis DNA and protein synthesis.
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Formycin- 5- triphosphate which incorporated into DNA and codes similar to ATP.
Both antibiotics serve as substrates for many enzymes which act on adenosine or ATP.
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Formycin B is a nucleoside analouge for inosine (is not phosphorylated) and inhibit purine phosphrylase and can supress viral growth.
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Antibiotics and inhibition of DNA synthesis
e.g. Azaserine and diazooxo-L- nor leucine (DON) as an analouge to L. glutamine. Azaserine DON
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e.g. formycin , tubercidin as adenosine analouges.
Incorporation of several nucleoside antibiotics resulting in the formation of ineffective nucleic acids. e.g. formycin , tubercidin as adenosine analouges. Tubercidin
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Cordycepin, after intracellular phosphorylation to triphosphate becomes incorporated at the growing 3-end of RNA chains and as it lacks the free hydroxyl group at the 3 carbon, further elongation of the chain is blocked.
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Interference with polymerization process:
Some antibiotics are known to bind polymerization enzymes and inhibits their activities. RNA polymerase DNA polymerase
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Some antibiotics cross-linked by covalent bond with DNA.
e.g. Mitomycin
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Hadacidin is a structural analouge of L-aspartic acid and it inhibits adenyl succinate synthetase enzyme which catalyses the first step in the conversion of IMP ………… AMP
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Intercalation: i.e Binding with DNA itself e.g. Actinomycin D and anthracyclins. Inhibition of transcription: Chromomycin and distamycin A inhibits transcription. Degradation of DNA e.g. Streptozotocin
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