Lincomycin structure

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. 

In traditional electrophoresis, separation efficiency is limited by thermal diffusion and convection. Owing to long analysis times and low efficiencies, these procedures never enjoyed wide usage. Problems have arisen when trying to differentiate between structurally related drug residues such as streptomycin and dihydrostreptomycin, tetracyclines, lincomycin and clindamycin, and erythromycin and oleandomycin (83, 84). To overcome these problems, anticonvective media, such as polyacrylamide or agarose gels, have also been used. 

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. 

Antibiotic Bu-2545, 7-0-methyl-4 -depropyllincomycin (1, R = OCH. R = H 3 but lacking the 4 propyl group). Clf,H jIV>Or,S. produced by Streptotnycex strain No. H 230-5. possesses structural features in common with both celesticetin and lincomycin. 

Clindamycin is a chlorine-substituted derivative of lincomycin, an antibiotic that is elaborated by Streptomyces lincolnensis. Lincomycin, although structurally distinct, resembles erythromycin in activity, but it is toxic and no longer used. 

R, D. Birkenmeyer and F. Kagan, Lincomycin. XI. Synthesis and structure of clindamycin, a potent antibacterial agent, J. Med. Chem. 13 616 (1970). 

Carbohydrate derivatives with anomeric sulfur are not very common in nature, the only examples found are the various glucosinolates ( mustard oil glycosides ) mainly from the Bras-sicaceae family [1,2,3], the simple alkyl thioglycosides of lincomycin and structurally relat-... 

Martin, Y.C. and Lynn, K.R. (1971). Quantitative Structure-Activity Relationships in Leucomy-cin and Lincomycin Antibiotics. J.Med.Chem., 14,1162-1166. 

Structural studies showed that lincomycin consists of a carbohydrate portion, methyl 6 - amino - 6,8 -dideoxyl - 1 -... 

C NMR Spectrum and Spin - Lattice relaxation times were used to study the structure of lincomycin (24). The results of analysis are reported in Table (III) and Figure (V). The signal assignments were based on spectral comparison of the structured related compounds and on other known techniques. 

Enzymatic hydrolysis rates for different positional and structural esters of lincomycin were determined in dog serum and simulated USP intestinal fluid (75). In general, the hydrolysis rates were faster in simulated intestinal fluid than in dog serum, indicating a higher esterase activity in simulated intestinal fluid. The 2- propionate ester of lincomycin was hydrolyzed slower than the longer chain 2 hexanoate ester, with the greatest difference in rates occuring in simulated intestinal fluid. Sterically hindered esters were hydrolyzed at extremely slow rates. 

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. 

Wilhelm, J. M., Oleinick, N. L., and Corcoran, J. W. (1968). Interaction of antibiotics with ribosomes Structure-function relationships and a possible common mechanism for the antibacterial action of the macrolides and lincomycin. Antimicrob. Agents Chemother. 1967, 236-249. 

Structures analogous to the tyrosine-derived portion of anthramycin are to be seen in the propyl- and ethyl-proline moieties of lincomycin (167) and (168), which are produced by another Streptomyces species. These substituted proline residues had been shownearlier to arise from tyrosine too C-1 of tyrosine was incorporated efficiently and specifically into the carboxy-groups of (169) and (170), and a study showed that the nitrogen atom of the proline ring came from... 

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]. 

Methyl penta-A,0-acetyl-a-D-lincosaminide, related to lincomycin (55, X=OH), has been prepared from myo-inosotol/ Lincomycin has been converted by a double inversion sequence via the chloride (clindamycin) into the analogues 55, X=N3, imidazol-2-thiyl, etc/ and the lincosamine-related structure 56 has been made from l,2 3,4-diO-isopropylidene-D-galactose/ ... 

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