Synthesis and structure-activity relationships of truncated bisubstrate inhibitors of aminoglycoside 6'-N-acetyltransferases - PubMed (original) (raw)

. 2006 Aug 24;49(17):5273-81.

doi: 10.1021/jm060732n.

Affiliations

Synthesis and structure-activity relationships of truncated bisubstrate inhibitors of aminoglycoside 6'-N-acetyltransferases

Feng Gao et al. J Med Chem. 2006.

Abstract

Truncated aminoglycoside-coenzyme A bisubstrate analogues were efficiently prepared using a convergent approach where the amine and the thiol are coupled in one pot with the addition of a linker, without the need for protecting groups. These derivatives were tested for their effect on the activity of the resistance-causing enzyme aminoglycoside 6'-N-acetyltransferase Ii, and key structure-activity relationships are reported. Moreover, one of the inhibitors is able to block aminoglycoside resistance in cells expressing this enzyme.

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