气候变化领域集成服务门户(CCPortal): A Sos proteomimetic as a pan-Ras inhibitor

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DOI	10.1073/pnas.2101027118
	A Sos proteomimetic as a pan-Ras inhibitor
	Hong S.H.; Yoo D.Y.; Conway L.; Richards-Corke K.C.; Parker C.G.; Arora P.S.
发表日期	2021
ISSN	00278424
卷号	118 期号:18
英文摘要	Aberrant Ras signaling is linked to a wide spectrum of hyper-proliferative diseases, and components of the signaling pathway, including Ras, have been the subject of intense and ongoing drug discovery efforts. The cellular activity of Ras is modulated by its association with the guanine nucleotide exchange factor Son of sevenless (Sos), and the high-resolution crystal structure of the Ras-Sos complex provides a basis for the rational design of orthosteric Ras ligands. We constructed a synthetic Sos protein mimic that engages the wild-type and oncogenic forms of nucleotide-bound Ras and modulates downstream kinase signaling. The Sos mimic was designed to capture the conformation of the Sos helix-loop-helix motif that makes critical contacts with Ras in its switch region. Chemoproteomic studies illustrate that the proteomimetic engages Ras and other cellular GTPases. The synthetic proteomimetic resists proteolytic degradation and enters cells through macropinocytosis. As such, it is selectively toxic to cancer cells with up-regulated macropinocytosis, including those that feature oncogenic Ras mutations. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Peptide; Proteomimetic; Ras; Sos
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179695
作者单位	Department of Chemistry, New York University, New York, NY 10003, United States; Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458, United States
推荐引用方式 GB/T 7714	Hong S.H.,Yoo D.Y.,Conway L.,et al. A Sos proteomimetic as a pan-Ras inhibitor[J],2021,118(18).
APA	Hong S.H.,Yoo D.Y.,Conway L.,Richards-Corke K.C.,Parker C.G.,&Arora P.S..(2021).A Sos proteomimetic as a pan-Ras inhibitor.Proceedings of the National Academy of Sciences of the United States of America,118(18).
MLA	Hong S.H.,et al."A Sos proteomimetic as a pan-Ras inhibitor".Proceedings of the National Academy of Sciences of the United States of America 118.18(2021).