跳转至内容
Merck
  • Synthesis and structure-activity relationships of truncated bisubstrate inhibitors of aminoglycoside 6'-N-acetyltransferases.

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

Journal of medicinal chemistry (2006-08-18)
Feng Gao, Xuxu Yan, Tushar Shakya, Oliver M Baettig, Samia Ait-Mohand-Brunet, Albert M Berghuis, Gerard D Wright, Karine Auclair
摘要

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.