Stereochemical Promiscuity in Artificial Transcriptional Activators

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• 作者：Sara J. Buhrlage ; Brian B. Brennan ; Aaron R. Minter ; and Anna K. Mapp
• 刊名：Journal of the American Chemical Society
• 出版年：2005
• 出版时间：September 14, 2005
• 年：2005
• 卷：127
• 期：36
• 页码：12456 - 12457
• 全文大小：98K
• 年卷期：v.127,no.36(September 14, 2005)
• ISSN：1520-5126

文摘

Small molecule replacements of transcriptional activation domains are highly desirable targets due to their utility as mechanistic tools and their long-term therapeutic potential for a variety of human diseases. Here, we examine the ability of amphipathic isoxazolidines differing only in the placement of constituent side chains to function as transcriptional activation domains. The results reveal that precise positioning of functional groups within a conformationally constrained small molecule scaffold is not required for transcription function; rather, the balance of polarity and hydrophobicity within the scaffold is the more important determinant of transcription function. This suggests that a number of different organic molecule scaffolds should function as transcriptional activator domains when appropriately functionalized, a hypothesis currently under investigation.