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Dr.Elza Joy Munjely
JR-I
Depmt. Of Pharmacology
Govt. Medical College,Kottayam.
2
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.
3
PROKARYOTIC AND EUKARYOTIC RIBOSOMES
PROTEIN SYNTHESIS
PROCESS OF TRANSLATION
30 S
50S
P-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
A
5
TRANSLOCATION
A4
A3
A2
A1
A
5
TRANSLOCATION
A4
A3
A2
A1
A
5
A
6
MOA OF AMINOGLYCOSIDES &
SPECTINOMYCIN
 Penetrate bacterial cell wall through porin channels by
passive diffusion
 Betalactams facilitate passive diffusion of
aminoglycosides-SYNERGISTIC ACTION
Bind to 30S ribosomal subunit
Improper formation of initiation complex
Misreading of mRNA
30 S
50S
P-Site A-Site
IMPROPER FORMATION OF INITIATION
COMPLEX & MISREADING OF mRNA
m-RNA
AMINOGLYCOSIDES
&SPECTINOMYCIN
MOA OF LINEZOLID
 Binds to 50S ribosomal subunit near the interface with
30S subunit.
 Prevents the formation of ribosomal complex.
50S
P-Site A-Site
LINEZOLID
INHIBITION OF RIBOSOMAL COMPLEX
FORMATION
MOA OF TETRACYCLINES
 Drug 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 tRNA
TO A SITE
MOA OF CHLORAMPHENICOL
 Binds to 50S subunit of the ribosome
 Inhibits 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 ribosome
 Thus inhibits translocation
A4
A3
A2
A1
P-Site A-Site
MACROLIDES ,
CLINDAMYCIN &
STREPTOGRAMINS
TRANSLOCATION INHIBITED
MOA OF MUPIROCIN
 Binds to isoleucyl tRNA synthetase
 Prevents incorporation of isoleucine into bacterial
protiens
THANK YOU

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