lincomycin brands

Molecular formula: C18H34N2O6S

Lincomycin contains the unusual amino acid moiety propyl hygric acid linked to the sugar moiety α-methylthiolincosamine (α-MTL) that, like other lincosamides, functions as a structural analogue of the 3' end of L-Pro-Met-tRNA and deacylated-tRNA to interact with the 23S rRNA of the 50S bacterial ribosomal subunit. Detailed investigations into the mechanism of the related lincosamide [clindamycin] suggested a two-phase binding, instantaneously to the A-site with a shift in equilibrium towards the P-site over several seconds. This shift appears to be due to rotation of the propyl hygric acid moiety, while the α-MTL remains relatively stationary. Recent crystal structures of lincomycin in complex with the 50S ribosomal subunit of _Staphylococcus aureus_ show that the α-MTL moiety forms hydrogen bonds with C2611, A2058, G2505, A2059, and G2503 of the 23S rRNA while the propyl hygric acid moiety interacts only through van der Waals contacts, suggesting it may be free to rotate similar to [clindamycin]. This mechanism is supported by the observation that the most common resistance mechanism, which also affects macrolides and streptogramin B (MSLB resistance) involves methylation of A2058; other resistance mechanisms similarly target residues such as A2058, A2059, and C2611. Lincomycin may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Lincomycin appears to inhibit protein synthesis in susceptible organisms by binding to 50S ribosomal subunits; the primary effect is inhibition of peptide bond formation. The site of action appears to be the same as that of clindamycin, erythromycin, and chloramphenicol. /The authors/ ... investigated the inhibition of peptide bond formation by the antibiotic lincomycin, at 150 mM NH4Cl. /The authors/ ... used an in vitro system in which a ribosomal ternary complex, the acetyl[3H] phenylalanine-tRNA-70 S ribosome-poly(U) complex (complex C), reacts with puromycin, forming peptide bonds. Complex C can be considered an analog of the elongating ribosomal complex and puromycin an analog of aminoacyl-tRNA. In a previous study /the authors/ ... reported on the kinetics of inhibition by lincomycin at 100 mM NH4Cl. In the present investigation, /the authors/ ... find that an increase of the ammonium ion concentration to 150 mM causes profound changes in the kinetic behavior of the system, which can be summarized as follows. First, the association rate for complex C and lincomycin is increased. At a lincomycin concentration of 10 uM the apparent equilibration rate constant is 4.3 min-1 at 100 mM NH4Cl, whereas it becomes 6.7 min-1 at 150 mM. Second, at 150 mM NH4Cl, with increasing concentrations of lincomycin, there is a transition from competitive to mixed-noncompetitive inhibition. The prevailing notion is that lincomycin acts at the ribosomal A-site, a mechanism that agrees only with competitive kinetics (mutually exclusive binding between puromycin and lincomycin). At the molecular level, the change in the kinetics of inhibition that we observe may mean that the mutually exclusive binding between aminoacyl-tRNA and lincomycin is converted to simultaneous binding, as a result of conformational changes occurring in the elongating ribosomal complex.

Source: PubChem (NCBI) · compound 3000540