Targeted Protein Degradation by Chimeric Small Molecules, PROTACs and SNIPERs
نویسندگان
چکیده
منابع مشابه
Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation.
The intracellular levels of many proteins are regulated by ubiquitin-dependent proteolysis. One of the best-characterized enzymes that catalyzes the attachment of ubiquitin to proteins is a ubiquitin ligase complex, Skp1-Cullin-F box complex containing Hrt1 (SCF). We sought to artificially target a protein to the SCF complex for ubiquitination and degradation. To this end, we tested methionine ...
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The current predominant therapeutic paradigm is based on maximizing drug-receptor occupancy to achieve clinical benefit. This strategy, however, generally requires excessive drug concentrations to ensure sufficient occupancy, often leading to adverse side effects. Here, we describe major improvements to the proteolysis targeting chimeras (PROTACs) method, a chemical knockdown strategy in which ...
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Development of novel small molecules that selectively degrade pathogenic proteins would provide an important advance in targeted therapy. Recently, we have devised a series of hybrid small molecules named SNIPER (specific and nongenetic IAP-dependent protein ERaser) that induces the degradation of target proteins via the ubiquitin-proteasome system. To understand the localization of proteins th...
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Many proteins are transported from the nucleus to the cytoplasm by the exportin CRM1, which recognizes cargo proteins through a leucine rich nuclear export signal (NES). This nuclear export process can be inhibited by several small molecules, both natural products and fully synthetic compounds. The structural basis for the inhibition of nuclear export by leptomycin (LMB) based on disruption of ...
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ژورنال
عنوان ژورنال: Frontiers in Chemistry
سال: 2019
ISSN: 2296-2646
DOI: 10.3389/fchem.2019.00849