合成 7-苄基鸟苷帽类似物缀合物用于 eIF4E 靶向降解。
Synthesis of 7-benzylguanosine cap-analogue conjugates for eIF4E targeted degradation.
机构信息
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, 1600 Huron Parkway, Ann Arbor, MI, 48109, USA.
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, 1600 Huron Parkway, Ann Arbor, MI, 48109, USA.
出版信息
Eur J Med Chem. 2019 Mar 15;166:339-350. doi: 10.1016/j.ejmech.2019.01.080. Epub 2019 Jan 31.
Abstract
Eukaryotic translation initiation factor 4E (eIF4E) is a key player in the initiation of cap-dependent translation through recognition of the mGpppX cap at the 5' terminus of coding mRNAs. As eIF4E overexpression has been observed in a number of human diseases, most notably cancer, targeting this oncogenic translation initiation factor has emerged as a promising strategy for the development of novel anti-cancer therapeutics. Toward this end, in the present study, we have rationally designed a series of BnGxP-based PROTACs for the targeted degradation of eIF4E. Herein we describe our synthetic efforts, in addition to biochemical and cellular characterization of these compounds.
摘要
真核翻译起始因子 4E（eIF4E）通过识别编码 mRNA 5' 末端的 mGpppX 帽，在帽依赖性翻译的起始中起着关键作用。由于 eIF4E 的过表达已在许多人类疾病中观察到，尤其是癌症，因此靶向这种致癌翻译起始因子已成为开发新型抗癌治疗药物的有前途的策略。为此，在本研究中，我们合理设计了一系列基于 BnGxP 的 PROTACs，用于靶向降解 eIF4E。在此，我们描述了我们的合成工作，以及对这些化合物的生化和细胞特性的描述。
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