Reaction mechanism of macrolide 2'-phosphotransferase [MPH(2')] from Escherichia coli to the 2'-modified macrolide antibiotics was analyzed by using microbioassay, nuclear magnetic resonance (NMR) spectrometric assay and mass spectrometry. It was found by microbioassay that the 2'-modified macrolide antibiotics as triacetyloleandomycin (TAO), erythromycin ethyl succinate (EME) and erythromycin estolate were inactivated with adenosine triphosphate (ATP) by MPH(2'). The NMR spectrometric assay for the analysis of the reaction with the 2'-modified macrolide antibiotics and MPH(2') was established using guanosine triphosphate, which was higher reaction rate than ATP, as a cofactor. It was clearly shown by NMR spectrometric assay and mass spectrometry that the C2'-side chain of TAO and EME was naturally released in phosphate buffer solution, and then, the C2' position was phosphorylated with GTP by MPH(2').
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Biomaterials
October 2012
Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
One of the most common life-threatening infections in immunosuppressive patients, like AIDs patients, is cryptococcal meningitis or meningoencephalitis. Current therapeutic options are mostly ineffective and mortality rates remain high. Hydrophobic antifungal drug Amphotericin B (AmB), has become a golden standard in severe systemic fungal infection therapy.
View Article and Find Full Text PDFJ Control Release
October 2010
Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
Amphotericin B (AmB) is a poorly water soluble antibiotic and is used to treat fungal infections of the central nervous system (CNS). However, AmB shows poor penetration into the CNS. Angiopep-2, the ligand of low-density lipoprotein receptor-related protein (LRP) present on the BBB, exhibits higher transcytosis capacity and parenchymal accumulation, which allowed us to consider the selectivity of it for receptor-mediated drug targeting to the brain.
View Article and Find Full Text PDFJpn J Antibiot
September 1993
Department of Microbiology, Tokyo College of Pharmacy.
Reaction mechanism of macrolide 2'-phosphotransferase [MPH(2')] from Escherichia coli to the 2'-modified macrolide antibiotics was analyzed by using microbioassay, nuclear magnetic resonance (NMR) spectrometric assay and mass spectrometry. It was found by microbioassay that the 2'-modified macrolide antibiotics as triacetyloleandomycin (TAO), erythromycin ethyl succinate (EME) and erythromycin estolate were inactivated with adenosine triphosphate (ATP) by MPH(2'). The NMR spectrometric assay for the analysis of the reaction with the 2'-modified macrolide antibiotics and MPH(2') was established using guanosine triphosphate, which was higher reaction rate than ATP, as a cofactor.
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