Regio- and chemoselective 6′-N-derivatization of aminoglycosides: Bisubstrate inhibitors as probes to study aminoglycoside 6′-N- acetyltransferases

Abstract

(Chemical Equation Presented) Complex nanomolar inhibitors in one pot: Aminoglycoside-coenzyme A derivatives were prepared through an efficient regioselective 6′-N modification of aminoglycosides (see scheme). These bisubstrates show tight-binding competitive inhibition of aminoglycoside 6′-N-acetyltransferase, an enzyme involved in antibiotic resistance. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.