Synthesis of a phosphonate-linked aminoglycoside-coenzyme a bisubstrate and use in mechanistic studies of an enzyme involved in aminoglycoside resistance.

ABSTRACT: Just five steps! The synthesis of a phosphonate-linked aminoglycoside-coenzyme A derivative (see scheme) that includes a Michael addition in water has been realized in just five steps. Aminoglycoside N-6'-acetyltransferases (AAC(6')s) are important determinants of antibiotic resistance. A good mechanistic understanding of these enzymes is essential to overcome aminoglycoside resistance. We have previously reported the synthesis of amide- and sulfonamide-linked aminoglycoside-coenzyme A conjugates, which were useful mechanistic and structural probes of AAC(6')s. We report here the synthesis of a phosphonate-linked aminoglycoside-coenzyme A variant, which is expected to be a superior mimic of the tetrahedral intermediate proposed for catalysis by AAC(6')s. This synthetic target is especially

SUBMITTER: Gao F 

PROVIDER: S-EPMC3084187 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature