Lincomycin chemical structure

Lincomycin. The lincomycins and celesticetins are a small family of antibiotics that have carbuliydrate-lype structures. Clindamycin, a chemical modification of lincomvcin, is clinically superior, Antibiotics in this family inhibit gram-positive aerobic and anaerobic bacteria by interfering with protein biosynthesis. 

H). C,8H34N206S. the first lincosaminide antibiotic to which a structure was assigned, is defined chemically as methyl 6,8-dideoxy-6-(l-methyl-fro/M-4-propyl-L-pyrrolidin-2-ylcarbonylamino)-l-thio-D-erythro-L>-gal-actu-octopyranoside. Both lincomycin and the semisynthetic clindamycin (I, R = H, R = Cl), CisH ClNjOsS, are widely used in clinical practice. The trivial name of the sugar fragment of this antibiotic, methyl a-thiolincosaminide, has lent itself to the other members of this family, whether produced as secondary metabolites of soil microorganisms or derived semisynthetically by chemical modification. 

Lincomycin, an antibiotics produced by Streptomyces lincolnensis, has been used widely in the treatment of infections caused by gram positive organisms. Lincomycin inhibited microbial protein synthesis by interacting strongly and specifically with the 50 S ribosomal subunit at mutually related sites. The results show that such interaction was not influenced by any of the chemical modifications of lincomycin structure. One molecule of antibiotic bound per 50 S subunit. It inhibited peptide bond formation, a mixture of protein synthesis which was catalyzed by a peptidyl transferase centre on the 50 S subunit. It interfered with substrate binding at the P- or A- site on the catalytic centre. It probably bound to the ribosome in positions at or close to the peptide transferase centre. 

The successes achieved in the past decade with chemically modified penicillins, tetracyclines, and lincomycin, undoubtedly influenced the judgment of the panel that preparation of structural analogs of useful antibiotics by chemical or other means should be ranked as one of the two most promising discovery approaches for the next decade. Before proceeding further with the evaluation made by the respondents of the five approaches (Table VII), some aspects of the history and nature of the structural modification approach are examined. 

The clinically important antibiotic lincomycin [1, 2] exerts its antibacterial activity by the inhibition of protein synthesis at the ribosomal level. A study of the structure of lincomycin by Hoeksema and co-workers [3] employing both classical chemical degradation and nuclear magnetic resonance data, led to the announcement of the structure of the molecule. Lincomycin proved to be a member of a new class of antibiotics characterized by an alkyl 6-amino-6,8-dideoxy-l-thio-D-erythro OL-D-galacto-octopymno- side joined with the proline moiety by an amide linkage (Fig. 1). 

Further details of chemical characterization and nuclear magnetic resonance data as well as ab initio calculations on lincomycin and related structures subsequently appeared [4-10]. For early reviews on lincomycin subject see Refs. [11, 12]. 

Hocksema H, Bannister B, Birkenmeyer RD, Kagan F, Magerlein B], MacKellar FA, Schtoeder W, Slomp O, Herr RR. Chemical studies on lincomycin. I. The structure of lincomycin. J Am Chem Soc 1964 86 4223-4224. 

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