Platensimycin CAS NO 835876-32-9 Inquire about Platensimycin

Tecoland supplies Platensimycin bulk active pharmaceutical ingredient (API) to the pharmaceutical industry. Our Platensimycin is manufactured by cGMP compliant facility. Welcome to contact us for further details including current DMF status for the product and up to date regulatory status of the manufacturing facility. We look forward to assisting you with your research and development projects.
What is Platensimycin?Platensimycin

Platensimycin, a metabolite of Streptomyces platensis, which is an excellent example of a unique structural class of natural antibiotics, has been demonstrated to be a breakthrough in recent antibiotic research due to its unique functional pattern and significant antibacterial activity. This compound is a member of a class of antibiotics which act by blocking enzymesinvolved in the condensation steps in fatty acidbiosynthesis, which Gram-positive bacterianeed to biosynthesise cell membranes. Other enzymes in this pathway have similarly been proven antibiotic targets for example FabI, the enoyl-ACP (acyl carrier protein) reductase, that is inhibited by isoniazidand related compounds and the antiseptic agent triclosan.

Mechanism of Action:

Platensimycin has shown good activity against a panel of Gram positive organisms which included various resistant strains. Platensimycin works by inhibiting beta-ketoacyl synthases which are key enzymes in the production of fatty acids required for bacterial cell membranes. Here is the possible mechanism of action: Firstly, the thiol group of FabF Cys163 is activated through the dipole moment of helix N-alpha-3 which lowers the pKaof this functional group. The nucleophilicity of the cysteine is facilitated by an oxyanion hole formed with the backbone amides of Cys163 and Phe400. The crystal structure complex with platensimycin employed a C163Q mutant which gave a 50-fold increase in apparent binding. The Gln163 residue lies adjacent to the carboxylate of platensimycin but makes no specific hydrogen bond. Given the close proximity of the carboxylate of platensimycin (presumed to be an anion) to the anionic thiol of Cys163 in the wild type enzyme may suggest the reason behind the increase in binding of the C163Q mutant. The second set of residues worth considering comprises His303 and His340 which play a role in the decarboxylation mechanism of the malonyl moiety. In particular, His303 activates a structured water to attack the carboxylate of the incoming malonyl-ACP.The crystal structure of FabF also demonstrates that His340 forms a hydrogen bond between the amide nitrogen of Leu342 and the N-delta- atom of the imidazole ring meaning that the lone pair must reside on this atom [1,18]. In the platensimycin crystal structure the structured water adjacent to His303 is no longer present which may suggest an alternative electronic state for this residue. A strong possibility exists that His303 would present itself as a cation capable of forming an ionic interaction with the benzoic acid group of platensimycin.

Clinical use:

Platensimycin is an experimental new drug in preclinical trials in an effort to combat MRSA in a mouse model. Platensimycin is a very effective antibiotic in vivo when continuously administered to cells, however this efficacy is reduced when administered by more conventional means. Consequently, and in light of the elevated levels of the drug necessary for effectiveness, clinical trials have been delayed pending the development of variants of similar chemical form which have more favorable properties. Since the importance of platensimycin, it has been studied to improve the production by gene regulation and it is also emphasized recently to investigate the tolerance of modification without affecting activity by chemical modifications,which can hopefully create the easier synthetic pathway or increase the activity of platensimycin.


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