A protein synthesis inhibitor is a substance that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins. All of the antibiotics that target bacterial protein synthesis do so by interacting with the bacterial ribosome and inhibiting its function. The ribosome might not seem like a very good target for selective toxicity, because all cells, including our own, use ribosomes for protein synthesis.The good thing is that bacteria and eukaryotes have ribosomes that are structurally different. Bacteria have so-called 70S ribosomes and eukaryotes have 80S ribosomes. No, not '70s and '80s ribosomes, although that would be pretty entertaining. The S stands for 'Svedberg unit,' and it refers to the rate at which particles sediment down into the tube during high-speed ultracentrifugation. Basically, it tells us about the ribosome's molecular weight and shape.
70S and 80S ribosomes are different enough that antibiotics can specifically target one and not the other. Let's take a closer look at the bacterial 70S ribosome and see where some different kinds of antibiotics act on it. Remember that ribosomes are made of RNA and protein and that they have two subunits, one large and one small.
The bacterial 70S ribosome's subunits are the 50S subunit and the 30S subunit. Yes, I know, 50 + 30 = 80, not 70, but this is not a math mistake. Using the Svedberg unit to measure ribosomes means that things don't always add up perfectly, because rates of sedimentation are not additive like molecular weights are.
Before we get into the specifics of how antibiotics inhibit bacterial ribosomes, let's briefly review how ribosomes work. First, a tRNA loaded with a particular amino acid enters the ribosome at the A site. The tRNA's anticodon has to match the codon, or group of three nucleotides on the mRNA. Then, at the P site of the ribosome, a peptide bond forms between the previous amino acid and the new amino acid. Finally, the empty tRNA exits at the E site. This process repeats for the whole length of the mRNA, and the polypeptide chain continues to grow.
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NUM CONTENT SLIDE
1 INTRODUCTION TO PROTEIN SYNTHESIS 4
2 PROKARYOTIC AND EUKARYOTIC RIBOSOMES 5
3 GENERAL MECHANISM OF ANTIBIOTIC 6
4 CLASSIFICATION OF PROTEIN SYNTHESIS INHIBITORS 7
5 THERAPEUTIC APPLICATIONS OF TETRACYCLINES 8
6 THERAPEUTIC APPLICATIONS OF MACROLIDES 9
7 THERAPEUTIC APPLICATIONS OF LINEZOLID AND ADMINISTRATION
MACROLIDE ANTIBIOTICS
10
8 PROTEIN SYNTHESIS IN RIBOSOMES 11
9 GENERAL MECHANISM OF PROTEIN SYNTHESIS INHIBITORS 12,13
10 MECHANISM OF TETRACYCLINES 14
11 MECHANISM OF AMINOGLYCOSIDES 15
12 MECHANISM OF ERYTHROMYCIN AND CLINDAMYCIN 16
13 MECHANISM OF CHLORAMPHENICOL 17
14 MECHANISM OF LINEZOLID 18
15 PHARMACOKINETICS OF SOME PROTEIN SYNTHESIS INHIBITORS AND
ADVERSE EFFECTS OF TETRACYCLINE
19
16 SOME ADVERSE EFFECTS OF MACROLIDE AND AMINOGLYCOSIDES
ANTIBIOTICS
20
17 DRUG INTRACTION OF PROTEIN SYNTHESIS INHIBITOR 21
3. 3
LEARNING OUTCOME
1. Able to understand the protein synthesis of
prokaryotic and eukaryotic.
2. List the common protein synthesis inhibitor drug
classification.
3. Abele to demonstrate the general mechanism of
common protein synthesis inhibitor.
4. Able to describe the common protein synthesis
inhibitor adverse effects.
5. Able to understand the therapeutic application of
protein synthesis inhibitor.
4. 4
1. INTRODUCTION TO PROTEIN SYNTHESIS
A protein synthesis inhibitor is a substance that stops
or slows the growth or proliferation of bacterial cells by
disrupting the processes to the generation of new
proteins by targeting the bacterial ribosome.
Protein synthesis inhibitors usually act at the ribosome
level, taking advantage of the major differences between
prokaryotic and eukaryotic ribosome structures.
Protein synthesis inhibitors work at different stages of
prokaryotic mRNA translation into proteins like initiation,
elongation (including aminoacyl tRNA entry,
proofreading, peptidyl transfer, and ribosomal
translocation), and termination.
Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D
5. 5
2. PROKARYOTIC AND EUKARYOTIC RIBOSOMES
CON…Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D
12. 9.GENERAL MECHANISM OF PROTEIN SYNTHESIS
INHIBITORS
Con…
12
Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D
13. 9.GENERAL MECHANISM OF PROTEIN SYNTHESIS
INHIBITORS
13
Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D
14. Tetracyclines binds
reversibly to the 30S subunit
of the bacterial ribosome,
thereby blocking access of
the amino acyl-tRNA to the
mRNA-ribosome complex at
the acceptor site.
By this mechanism,
bacterial protein synthesis is
inhibited
10. MECHANISM OF TETRACYCLINES
14
Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D
15. 15
11. MECHANISM OF AMINOGLYCOSIDES
•Susceptible gram-negative organisms
allow aminoglycosides to diffuse through
porin channels in their outer membranes.
•oxygen-dependent system that
transports the drug across the
cytoplasmic membrane.
•The antibiotic then binds to the 30S
ribosomal subunit prior to ribosome
formation.
•There, it interferes with assembly of the
functional ribosomal apparatus and/or
can cause the 30S subunit of the
completed ribosome to misread the
genetic code.
Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D
16. The macrolides bind irreversibly to
a site on the 50S subunit of the
bacterial ribosome, thus inhibiting
the translocation steps of protein
synthesis.
They may also interfere at other
steps, such as transpeptidation.
Generally considered to be
bacteriostatic, they may be
bactericidal at higher doses.
Their binding site is either
identical or in close proximity to
that for clindamycin and
chloramphenicol.
12.MECHANISM OF ERYTHROMYCIN AND CLINDAMYCIN
16
Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D
17. Chloramphenicol binds to the
bacterial 50S ribosomal
subunit and inhibits protein
synthesis at the peptidyl
transferase reaction.
Because of the similarity of
mammalian mitochondrial
ribosomes to those of
bacteria, protein synthesis in
these organelles may be
inhibited at high circulating
chloramphenicol levels,
producing bone marrow
toxicity.
13. MECHANISM OF CHLORAMPHENICOL
17 Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D
18. 18
The linezolid inhibits
bacterial protein
synthesis by inhibiting
the formation of the 70S
initiation complex.
Linezolid binds to a site
on the 50S subunit near
the interface with the
30S subunit
14. MECHANISM OF LINEZOLID
Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D
19. 19
15.PHARMACOKINETICS OF SOME PROTEIN SYNTHESIS
INHIBITORS AND ADVERSE EFFECTS OF TETRACYCLINE.
Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D
20. 20
16.SOME ADVERSE EFFECTS OF MACROLIDE
AND AMINOGLYCOSIDES ANTIBIOTICS
Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D