Lincosamides protein binding

Inhibition of protein synthesis through an action on certain subunits of microbial ribosomes (aminoglycosides, tetracyclines, chlorampenicol and its derivatives, macrolides and lincosamides). Each class of antimicrobial agent attaches to a different receptor site apart from macrolides and lincosamides, which bind to the same site on the 50S subunit of the microbial ribosome. 

Son, D. S., M. Osabe, M. Shimoda, and E. Kokue. 1998. Contribution of alpha-l-acid glycoprotein to species difference in lincosamides-plasma protein binding kinetics. Journal of Veterinary Pharmacology and Therapeutics 21 34—40. 

Macrolides, lincosamides and streptogramins are protein biosynthesis inhibitors that bind to 50S subunit of the ribosome and inhibit peptidyl tRNA translocation from the A-site to the P-site." Macrolides have a glycosylated 14-, 15- or 16-membered lactone ring structure and are produced by several species of Streptomyces. Lincosamide antibiotics were isolated initially from Streptomyces lincolnensis but later isolated from different species of Streptomcyces. Streptogramins were also isolated from Streptomycesgraminofaciens and subsequently from several different Streptomyces species. There are two structurally different streptogramins, A and B they are bacteriostatic individually and can be bactericidal when combined. 

Lincosamides (lincomycin and clindamycin) are representatives of a very small group of drugs synthesized up of an amino acid bound to an amino sugar. Lincosamides bind with the 50 S ribosomal subunit of bacteria and inhibit protein synthesis. They also inhibit pep-tidyltransferase action. Lincosamides are bacteriostatic antibiotics however, when they reach a certain level in the plasma, they also exhibit bactericidal action against some bacteria. Lincosamides are highly active against anaerobic infections such as Peptococcus, Peptostreptococcus, Actinomyces, Propionibacterium, and Clostridium fringens, a few types of Peptococcus and Clostridium. 

Pharmacology Lincomycin and clindamycin, known collectively as lincosamides, bind exclusively to the 50 S subunit of bacterial ribosomes and suppress protein synthesis. Cross-resistance has been demonstrated between these 2 agents. Clindamycin is preferred because it is better absorbed and more potent. Pharmacokinetics Administration with food markedly impairs lincomycin (but not clindamycin) oral absorption. 

Macrolides and lincosamides have the same receptor site. They bind to the bacterial 50s ribosomal subunit, inhibiting protein synthesis and hence cell growth. Macrolides are usually bacteriostatic at low concentrations, but can become bactericidal for sensitive strains at high concentrations. 

The lincosamide family of antibiotics includes lin-comycin (Lincocin) and clindamycin (Cleocin), both of which inhibit protein synthesis. They bind to the SOS ri-bosomal subunit at a binding site close to or overlapping the binding sites for chloramphenicol and erythromycin. They block peptide bond formation by interference at either the A or P site on the ribosome. Lincomycin is no longer available for human use in the United States. 

Similar to macrolides, lincosamides also target the SOS ribosome subunit. More specifically, they inhibit the enzyme peptidyl transferase, which in turn inhibits the activity of ribosomes, preventing the binding of amino acyl-tRNA to the A site on the SOS subunit. That activity blocks the synthesis of proteins. 

Mecftantsm of Action A lincosamide antibacterial that inhibits protein synthesis of the bacterial cell wall by binding to bacterial ribosomal receptor sites. Topically, it decreases fatty acid concentration on the skin. Therapeutic Effect Bacteriostatic. Prevents outbreaks of acne vulgaris. 

For efficient extraction of macrolide and lincosamide residues from edible animal products, bound residues should be rendered soluble, most if not all of the proteins should be removed, and high recoveries for all analytes should be provided. Since tliese antibiotics do not strongly bind to proteins, many effective extraction methods have been reported. Sample extraction/deproteinization is usually accomplished by vortexing liquid samples or homogenizing semisolid samples with acetonitrile (136—139), acidified (136,140-142) orbasified acetonitrile (143), methanol (14, 144, 145), acidified (145-147) or basified methanol (148), chloroform (149-151), or dichloromethane under alkaline conditions (152). However, for extraction of sedecamycin, a neutral macrolide antibiotic, from swine tissues, use of ethyl acetate at acidic conditions has been suggested (153), while for lincomycin analysis in fish tissues, acidic buffer extraction followed by sodium tungstate deproteinization has been proposed (154). 

The MLS (macrolides, lincosamides, streptogramins) group of antibiotics all inhibit protein synthesis by binding to the 50S ribosomal subunit. Resistance mechanisms specific to individual members occur but resistance to all may be conferred by a single mechanism that involves 23S rRNA. However, it is claimed that the quinupristin-dalfopristin combination does not demonstrate cross-resistance to other antibiotics within the MLS group or to other antibiotics. 

It is widely accepted that MLS antibiotics inhibit protein synthesis by binding to closely related sites on the 508 subunit of the 70S ribosome of bacteria [4], despite being structurally different from each other (see Figs. 1 and 2 in a later section). That is the reason why, when inducible resistant Staphylococcus aureus cells are exposed to a low concentration of the drug (0.05 tg erythromycin/ml - 6.8 x 10 M), they show resistance against not only erythromycin but also other macrolide antibiotics as well as lincosamide and type B streptogramin antibiotics. Erythromycin has been widely used and has been the object of extensive molecular and biological studies. 

A. Classification and Pharmacokinetics The lincosamides lincomycin and clindamycin inhibit bacterial protein synthesis via a mechanism similar to that of the macrolides, though they are not chemically related. Mechanisms of resistance include methylation of the binding site on the 50S ribosomal subunit and enzymatic inactivation. Cross-resistance between lincosamides and macrolides is common. Good tissue penetration occurs after oral absorption. The lincosamides are eliminated partly by metabolism and partly by biliary and renal excretion. 

Chloramphenicol is bacteriostatic by virtue of inhibition of protein biosynthesis in both bacterial and, to a lesser extent, host ribosomes. Chloramphenicol binds to the SOS subparticle in a region near where the macrolides and lincosamides bind (Fig. 38.24). 

Chloramphenicol is a bacteriostatic agent that binds to the 508 ribosomal subunit and inhibits the transpeptidation in protein synthesis. While this agent is not widely used to treat staphylococcal infection, resistance to chloramphenicol is due to inactivation of the antibiotic by chloramphenicol acetyltransferase enzyme (CA7). Macrolides, such as erythromycin and oleandomycin lincosamides, such as lincomycin and clindamycin and streptogramin antibiotics also have a bacteriostatic effect on Staphylococcus spp. by binding to their 508 ribosomal subunit, arresting protein synthesis, but resistance to these antibiotics is also prevalent. Rifampin has also been used to treat staphylococcal infections, but when used alone, resistant strains quickly arise. 

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