Synthesis and Structure-Activity Relationships of Truncated Bisubstrate Inhibitors of Aminoglycoside 6'-N-Acetyltransferases

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• 作者：Feng Gao ; Xuxu Yan ; Tushar Shakya ; Oliver M. Baettig ; Samia Ait-Mohand-Brunet ; Albert M. Berghuis ; Gerard D. Wright ; Karine Auclair
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：August 24, 2006
• 年：2006
• 卷：49
• 期：17
• 页码：5273 - 5281
• 全文大小：144K
• 年卷期：v.49,no.17(August 24, 2006)
• ISSN：1520-4804

文摘

Truncated aminoglycoside-coenzyme A bisubstrate analogues were efficiently prepared using a convergentapproach where the amine and the thiol are coupled in one pot with the addition of a linker, without theneed 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.