Inhibiton of protien synthesis

Inhibition of protein synthesis
A notable difference between prokaryotic and eukaryotic cells is the structure of their ribosomes. The prokaryotic ribosome is composed of two subunits, small and large (30S and 50S, respectively).there are several steps in nucleic acid translation to protein .Different classes of antibiotics effect different steps in this sequence.
DNA mRNA Protien
transcription translation
(RNA synthesis) (protein synthesis)
Inhibitors of protein synthesis
-Aminoglycosides (bactericidal),-30S binding.
-Chloramphenicol ,macrolides, clindamycin (bacteriostatic)-50S binding ,- tetracyclines (bacteriostatic) -30S binding.
-Oxazolidnones- prevent 70S complex from being formed.
Aminoglycosides
The term aminoglycoside refers to a recognized medicinal and bacteriologic category of traditional Gram-negative antibacterial therapeutic agents that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). Aminoglycosides that are derived from bacteria of the Streptomyces genus are named with the suffix mycin, whereas those that are derived from Micromonospora are named with the suffix micin.(eg.,Gentamicin , Tobramycin, Streptomycin, Kanamycin, Netilmicin).




Structure of streptomycin
Character
1- Related in structure and function.
2-Drug differs based on location of radical groups attached to the 3 ring basic structure.
3- Rapid bactericidal effect.
4- Broad spectrum of action.
Route of entry
1. Outer Membrane entry:
Aminoglycosides are positively charged molecules which means they
rapidly enter bacteria (negatively charged).
2. Cytoplasmic Membrane entry:
The drugs cross the cytoplasmic membrane via respiratory enzymes
(involved in aerobic respiration).
Mode of action
The mode of action of streptomycin has been studied far more intensively than that of other aminoglycosides, but all probably act similarly. The first step is the attachment of the aminoglycoside to a specific receptor protein (P 12 in the case of streptomycin) on the 30S subunit of the microbial ribosome. Second, the aminoglycoside blocks the normal activity of the "initiation complex" of peptide formation (mRNA + formyl methionine + tRNA). Third, the mRNA message is misread on the "recognition region" of the ribosome; consequently, the wrong amino acid is inserted into the peptide, resulting in a nonfunctional protein. Fourth, aminoglycoside attachment results in the breakup of polysomes and their separation into monosomes incapable of protein synthesis.

Tetracycline
The first member of the group to be discovered is Chlortetracycline (Aureomycin) in the late 1940s, derived from a Streptomyces spp. They are a group of broad-spectrum antibiotics.
Tetracyclines bind to the 30S subunit of microbial ribosomes. They inhibit protein synthesis by blocking the attachment of charged aminoacyl-tRNA. Thus, they prevent introduction of new amino acids to the nascent peptide chain. The action is usually inhibitory and reversible upon withdrawal of the drug.


Structure of tetracycline
According to source:
• Naturally occurring
o Tetracycline
o Chlortetracycline
o Oxytetracycline
o Demeclocycline
o
• Semi-synthetic
o Doxycycline
o Lymecycline
o Meclocycline
o Methacycline
o Minocycline
o Rolitetracycline

Chloramphenicol
Chloramphenicol was originally derived from the Streptomyces venezuelae, and introduced into clinical practice in 1949, under the trade name Chloromycetin. It was the first antibiotic to be manufactured synthetically on a large scale. It is effective against a wide variety of Gram-positive and Gram-negative bacteria, including most anaerobic organisms.
Chloramphenicol is a bacteriostatic drug that stops bacterial growth by inhibiting protein synthesis. It binds to the 50S subunit of the ribosome ,and interferes with the binding of new amino acids to the nascent peptide chain, largely because chloramphenicol inhibits peptidyl transferase. Chloramphenicol is mainly bacteriostatic, and growth of microorganisms resumes when the drug is withdrawn.



Structure of chloramphenicol