On February 1, 2011, Cyrus, Kedra; Wehenkel, Marie; Choi, Eun-Young; Han, Hyeong-Jun; Lee, Hyosung; Swanson, Hollie; Kim, Kyung-Bo published an article.Application In Synthesis of Bis(2,5-dioxopyrrolidin-1-yl) glutarate The title of the article was Impact of linker length on the activity of PROTACs. And the article contained the following:
Conventional genetic approaches have provided a powerful tool in the study of proteins. However, these techniques often preclude selective manipulation of temporal and spatial protein functions, which is crucial for the investigation of dynamic cellular processes. To overcome these limitations, a small mol.-based novel technol. termed “PROteolysis TArgeting ChimeraS (PROTACs)” has been developed, targeting proteins for degradation at the post-translational level. Despite the promising potential of PROTACs to serve as mol. probes of complex signaling pathways, their design has not been generalized for broad application. Here, we present the first generalized approach for PROTAC design by fine-tuning the distance between the two participating partner proteins, the E3 ubiquitin ligase and the target protein. As such, we took a chem. approach to create estrogen receptor (ER)-α targeting PROTACs with varying linker lengths and the loss of the ER in cultured cells was monitored via western blot and fluorometric analyses. We found a significant effect of chain length on PROTAC efficacy, and, in this case, the optimum distance between the E3 recognition motif and the ligand was a 16 atom chain length. The information gathered from this experiment may offer a generalizable PROTAC design strategy to further the expansion of the PROTAC toolbox, opening new possibilities for the broad application of the PROTAC strategy in the study of multiple signaling pathways. The experimental process involved the reaction of Bis(2,5-dioxopyrrolidin-1-yl) glutarate(cas: 79642-50-5).Application In Synthesis of Bis(2,5-dioxopyrrolidin-1-yl) glutarate
The Article related to protein linker length breast cancer protac western blot fluorometry, Biochemical Methods: Other (Not Covered At Other Subsections) and other aspects.Application In Synthesis of Bis(2,5-dioxopyrrolidin-1-yl) glutarate
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