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

THANK YOU