Inhibitors of Protein Synthesis.pptVIP

Inhibitors of Protein Synthesis Bacterial cells are 50% protein by dry weight Inhibition of protein synthesis leads to cessation of growth or cell death Bacterial 70S ribosomes differ sufficiently from eukaryotic ribosomes to allow selective toxicity Other properties of the antibiotics still produce side effects. Ribosomes are cytoplasmic Drug must successfully enter and stay in the cytoplasm and exert effect. The antibiotics Families Aminoglycosides, macrolides, tetracyclines, etc. Individual drugs Chloramphenicol, clindamycin, mupirocin Variety of structures Mostly multi-ring nuclei with side chains Vary in effectiveness against different bacteria Variation not in site of attack but in successful entry into cells and variations in bacterial defense Review of Protein synthesis 30S subunit, Initiation factors, and mRNA come together. fMet-tRNA binds to mRNA 50S subunit binds to form initiation complex 2nd aminoacyl tRNA arrives at A site Amino acid transferred from 1st tRNA to aa of new tRNA peptide bond formed Uncharged tRNA moves to E site, then leaves Translocation of ribosome puts tRNA with growing chain in P site; elongation continues. Polysomes Representative sites of actions Aminoglycosides Mechanism of action for aminoglycosides Bactericidal, rare among protein synthesis inhibitors Transport through the wall, through PG of G+, through porins or through OM directly in G-, disrupting OM. Transport though cell membrane by carrier, using electrochemical gradient uses energy . Binds to ribosomes, keeping [free drug] low Combination of membrane damage and inhibition of protein synthesis is bactericidal Aminoglycoside enters cell Aminoglycosides cont. Aminoglycosides bind various sites on both ribosomal subunits Freeze translation after initiation step, prevent polysome formation Interfere with codon recognition, resulting in misreading Sometimes “cured” by ribosomal protein mutation Concentration dependent killing and post-antibiotic effect Related to membran