protien synthesis inhibitors by dr.elza
TRANSCRIPT
PROTIEN SYNTHESIS INHIBITORS
Dr.Elza Joy MunjelyJR-I
Depmt. Of Pharmacology Govt. Medical College,Kottayam.
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INTRODUCTION TO PROTEIN SYNTHESIS
• Protein synthesis inhibitor - substance that stops or slows the growth or proliferation of bacterial cells by disrupting the processes of generation of new proteins by targeting the bacterial ribosome.
• Act at the ribosome level• Take advantage of the major differences
between prokaryotic and eukaryotic ribosome.• Work at different stages of mRNA translation
like initiation, elongation, and termination.
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PROKARYOTIC AND EUKARYOTIC RIBOSOMES
PROTEIN SYNTHESIS
PROCESS OF TRANSLATION
30 S
50SP-Site A-Site
INITIATION COMPLEX
m-RNA
A4
P-Site A-Site
A3
A2
A1
TRANSPEPTIDATION
A4
P-Site A-Site
A3
A2
A1
A4
A3
A2
A1
A4
A3
A2
A1
A5
TRANSLOCATION
A4
A3
A2
A1
A5
TRANSLOCATION
A4
A3
A2
A1
A5
A6
MOA OF AMINOGLYCOSIDES & SPECTINOMYCINPenetrate bacterial cell wall through porin
channels by passive diffusionBetalactams facilitate passive diffusion of
aminoglycosides-SYNERGISTIC ACTION
Bind to 30S ribosomal subunit
Improper formation of initiation complex
Misreading of mRNA
30 S
50SP-Site A-Site
IMPROPER FORMATION OF INITIATION COMPLEX & MISREADING OF mRNA
m-RNA
AMINOGLYCOSIDES&SPECTINOMYCIN
MOA OF LINEZOLIDBinds to 50S ribosomal subunit near the
interface with 30S subunit.Prevents the formation of ribosomal complex.
50S
P-SiteA-SiteLINEZOLID
INHIBITION OF RIBOSOMAL COMPLEXFORMATION
MOA OF TETRACYCLINESDrug enter into cytoplasm by:
Energy dependent tetracycline active transport system – Gram positive bacteria
Passive diffusion through porin channels – Gram negative bacteria
Binds to 30Ssubunit of the ribosome& inhibits the binding of aminoacyl tRNA to
the A site.
A4
P-Site A-Site
A3
A2
A1
TETRACYCLINES
PREVENTS BINDING OF AMINOACYL tRNATO A SITE
MOA OF CHLORAMPHENICOLBinds to 50S subunit of the ribosomeInhibits peptide bond formation.
A4
P-Site A-Site
A3
A2
A1
TRANSPEPTIDATION INHIBITED
CHLORAMPHENICOL
MOA OF MACROLIDES ,CLINDAMYCIN &STREPTOGRAMINS
Reversibly binds to P site of 50 S ribosomeThus inhibits translocation
A4
A3
A2
A1
P-Site A-Site
MACROLIDES , CLINDAMYCIN &STREPTOGRAMINS
TRANSLOCATION INHIBITED
MOA OF MUPIROCINBinds to isoleucyl tRNA synthetasePrevents incorporation of isoleucine into
bacterial protiens
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