TRANSLATIONAL INHIBITORS

PRESENTED BY
VEDHA M
I MSc BIOCHEMISTRY
DEPARTMENT OF BIOCHEMISTRY
BHARATHIAR UNIVERSITY
 SYNOPSIS

• INTRODUCTION
• TRANSLATIONAL INHIBITORS
• MECHANISMS
• CONCLUSION
• REFERENCES
 INTRODUCTION

TRANSLATION

Translation is a process by which the genetic code contained within the

mRNA molecule is decoded to produce a specific amino acids in a
polypeptide chain.
 TRANSLATIONAL INHIBITORS

Translational inhibitors are the compounds

that stops or slows the growth (or)
proliferation of cells by disrupting the
process that leads directly to the generation
of new proteins.

A controlled translational process is required

for protein synthesis and normal cell
functioning but the substances like
chemicals , antibiotics and toxins affect one
or more steps involved in protein synthesis.
 WHY TRANSLATION IS
INHIBITED?

 In general , translation inhibition is one of the most common modes of

action that is crucial for restraining pathogenesis.

 Inhibitors targeting translation interfere with either assembly or the

processing of ribosomes or with proper utilisation of charged tRNAs
and translation factors .

 In simple terms, translation is inhibited to restrict the protein synthesis

that causes any adverse effects in case of any mutation or changes.
 INHIBITOR PROCESS AFFECTED SITE OF ACTION
STREPTOMYCIN INITIATION PROKARYOTES : 30s SUBUNIT
ELONGATION
NEOMYCIN PROTEIN SYNTHESIS PROKARYOTES : MULTIPLE
SITES
TETRACYCLINE AMINOACYL tRNA BINDING 30S/40S SUBUNITS
ERYTHROMYCIN TRANSLOCATION PROKARYOTES 50S SUBUNITS

PUROMYCIN PEPTIDE TRANSFER 70S/80S RIBOSOMES

FUSIDIC ACID TRANSLOCATION PROKARYOTES EF-G
CYCLOHEXIMIDE ELONGATION EUKARYOTES: 80S RIBOSOMES
RICIN ELONGATION EUKARYOTES: 60S RIBOSOMES
CHLORAMPHENICAL INHIBITS PEPTIDYL 50S SUBUNIT OF 70S
TRANSFERASE RIBOSOMES
PAROMOMYCIN INCREASES RIBOSOMAL RIBOSOMAL A-SITE
ERROR RATE
INHIBITORS INTERFERING WITH INITIATION :

 AMINOGLYCOSIDES
 LINEZOIDS
 OXAZOLIDINONES

AMINOGLYCOSIDES:
These antibiotics interfere with the initiation of protein synthesis and cause misreading of the mRNA code,
leading to incorrect protein synthesis.

LINEZOIDS:
Linezolid acts at the initiation stage ,probably by preventing the formation of the initiation complex, although the
mechanism is not fully understood.

OXAZOLIDINONES:
These antibiotics inhibit the initiation of protein synthesis by binding to the ribosome's 50S subunit.

8
INHIBITORS INTERFERING WITH RIBOSOMAL TRANSLOCATION :

 MACROLIDES
 CYCLOHEXIMIDE
 RICIN
 FUSIDIC ACID
MACROLIDES :
This group of antibiotics inhibits protein synthesis by blocking the translocation step, preventing the
ribosome from moving along the mRNA.

CYCLOHEXIMIDE:
This compound interferes with the translocation step of protein synthesis, preventing the ribosome from
moving along the mRNA.

FUSIDIC ACID :
It prevents the turnover of elongation factor G (EF-G) from the ribosome.

RICIN :
Ricin inhibits elongation by enzymatically modifying an rRNA of the eukaryotic 60S ribosomal subunit.
 INHIBITORS INTERFERING WITH PEPTIDYL TRANSFER :

 CHLORAMPHENICAL
 PLEUROMITILINS
 TRICHOTHECENE

CHLORAMPHENICAL :
This antibiotic inhibits the peptidyl transferase activity of the ribosome, preventing the formation of peptide
bonds during protein synthesis.

PLEUROMITILINS :
This class of antibiotics inhibits protein synthesis by binding to the ribosome's peptidyl transferase center,
blocking the elongation step.

TRICHOTHECENE :
Mycotoxins are potent and non selective inhibitors of peptide elongation .
INHIBITORS INTERFERING WITH AMINOACYL tRNA ENTRY :

 TETRACYCLINE :

These antibiotics block the binding of aminoacyl-tRNA to the ribosome, preventing elongation
of the polypeptide chain.

INHIBITORS INTERFERING TERMINATION :

 CLINDAMYCIN :
It causes premature dissociation of the peptidyl-tRNA from the ribosome

 STREPTOGRAMINS :
It causes premature release of the peptide chain.
MECHANISM OF ERYTHROMYCIN
MECHANISM OF TETRACYCLINE
Tetracycline binds to 30S
subunit

Screening of aminoacyl
tRNA

Blocks its
assembly in P-site

Release of tRNA

Protein synthesis
inhibited

Unproductive
hydrolysis of
GTP

Enormous drain of
energy in the cell
POTENTIAL OUTCOMES OF INHIBITING
TRANSLATION :

 CELLULAR DYSFUNCTION

 GENE EXPRESSION

 DRUG DEVELOPMENT

 MEDICAL APPLICATIONS
 The inhibitors target different steps of
the protein synthesis process, making

CONCLUSION>> them valuable tools in research and

potential therapeutic agents against
bacterial infections or in certain cases,
cancer treatment.
  Donald Voet, Judith G Voet, Charlotte
WPratt(2008) Fundamentals of Biochemistry,
3rd ed, USA:Jhon Wiley and sons
 Thomas.L.Devlin (2002) Textbook of
REFERENCES Biochemistry with clinical correlation,
5ed.NewYork: Wiley
 Liss>www.ncbi.nih.gov/pmc/articles/
PMC7229235
 https://en.m.wikipedia.org/wiki/
Protein_synthesis_inhibitor

20XX SAMPLE FOOTER TEXT 16

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