Expanding the Scope of Oligo-pyrrolinone鈥揚yrrolidines as Protein鈥揚rotein Interface Mimics

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• 作者：Arjun Raghuraman ; Dongyue Xin ; Lisa M. Perez ; Kevin Burgess
• 刊名：The Journal of Organic Chemistry
• 出版年：2013
• 出版时间：May 17, 2013
• 年：2013
• 卷：78
• 期：10
• 页码：4823-4833
• 全文大小：529K
• 年卷期：v.78,no.10(May 17, 2013)
• ISSN：1520-6904

文摘

Oligo-pyrrolinone鈥損yrrolidines (generic structure 1) have the potential to interfere with protein鈥損rotein interactions (PPIs), but to reduce this to practice it is necessary to be able to synthesize these structures with a variety of different side chains corresponding to genetically encoded proteins. This paper describes expansion of the synthetic scope of 1, the difficulties encountered in this process, particularly issues with epimerization and slow coupling rates, and methods to overcome them. Finally, spectroscopic and physicochemical properties as well as proteolytic stabilities of molecules in this series were measured; these data highlight the suitability of oligo-pyrrolinone鈥損yrrolidines for the development of pharmacological probes or pharmaceutical leads.