The kinetics of the alkaline degradation of daptomycin

✍ Scribed by Walaisiri Muangsiri; Lee E. Kirsch

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 183 KB
• Volume: 90
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.1060

✦ Synopsis

The aqueous degradation of daptomycin, a lipopeptide antibiotic, was investigated as a function of substrate concentration (0.5±10.0 mM), pH (9.0±10.5), buffer concentration (0.06± 0.20 M borate, glycinate, or carbonate buffers), temperature (20±508C), and ionic strength (0.1±0.8). The primary degradation pathway was determined by electrospray-mass spectroscopy (ES-MS), Fourier transform infrared (FTIR), and ¯uorescence spectroscopy to be hydrolysis of the ester linkage between the C-terminus (kynurenine) and the side chain of the fourth residue (threonine). The reaction was ®rst order with respect to time; however, the reaction order with respect to substrate concentration was 1 at substrate concentrations b 1 mM. Insigni®cant buffer effect was observed. The reaction was subject to speci®c base catalysis. Activation parameters were E a 13.6 kcal/KÁmol, DH { 13.0 kcal/KÁmol, and DS { À19.2 eu. The positive primary salt effect was observed with negative deviation at high concentration of salt. The magnitude of the salt effect depended on salt identities in the order sodium potassium `calcium chloride.