2010-10-01_ Matthews_2 - Antimicrobials II...

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Anti microbials II Inhibitors of Protein and Nucleic Acid Synthesis Jason Matthews Jason.matthews@utoronto.ca
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Protein synthesis 3 phases Initiation Elongation Termination Final step disassembly
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Ribosomal Complex Receive and translate genetic instructions to form specific proteins 2 subunits 30S and 50S Combine to form complete 70S ribosome fast ~20 amino acids/sec pro vs 2 a.a./sec euk Antimicrobials don’t bind to mammalian ribosomes Mammalian ribosomes 80S Exceptions – tetracyclines, chloramphenicol
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Alberts et al. Molecular Biology of the Cell 4 th edition Bacterial Eukaryotes
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Protein synthesis Initiation Where a functionally competent ribosome is assembled in the correct place on mRNA ready to commence protein synthesis Steps: Binding of 30S subunit with initiation factors Binding of the mRNA and the fMet tRNA » Formylmethionine fMet At this stage the 30S initiation complex is complete Binding of the 50S subunit and release of the initiation factors
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Protein Synthesis Elongation Whereby the correct amino acid is brought to the ribosome, is joined to the nascent polypeptide chain and the entire assembly moves one position along the mRNA. Steps: Cyclic process whereby new aminoacyl tRNA is positioned in the ribosome Amino acid is transferred to the growing polypeptide chain Whole assembly moves one position along
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Termination Which happens when a stop codon is reached, there is no amino acid to be incorporated and the newly synthesized polypeptide is released from the ribosome. Steps: Binding of release factors Hydrolysis of the peptidyl tRNA Disassembly - Final step in the cycle of protein synthesis Termination and Disassembly
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Antibiotics and Protein Synthesis 1. Aminoglycosides (gentamicin, tobramycin) 2. Tetracyclines (tetracycline, doxycycline) 3. Chloramphenicol 4. Macrolides (erythromycin) 5. Oxazolidinones (Linezolid)
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inhibit at several points Blocks normal activity of initiation complex Interferes with tRNA attachment Distorts triplet codon reading (misread) May have initial activity on bacterial cell membrane Create fissures resulting in leakage of intracellular contents Bactericidal activity X X X Streptomycin Aminoglycosides
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Streptomycin, neomycin, kanamycin, tobramycin, amikacin, netilmicin Developed for treatment of Gram
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This note was uploaded on 12/03/2010 for the course PHAMACOLOG pcl470 taught by Professor Arnot during the Fall '10 term at University of Toronto- Toronto.

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2010-10-01_ Matthews_2 - Antimicrobials II...

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