91656-99-4Relevant articles and documents
[2+2+2]-Cycloaddition of 4-Hydroxy-Substituted Enediynes to 2-Hydroxy-Substituted Decahydrophenanthrenes
Groth, Ulrich,Richter, Norbert,Kalogerakis, Aris
, p. 4634 - 4639 (2003)
Enediynes rac-4 were prepared in seven steps with an overall yield of 31% starting from 4-pentyn-1-ol (5). A cobalt mediated [2+2+2]-cycloaddition of these enediynes and subsequent removal of the metal fragment afforded the decahydrophenanthrenes rac-3/13
A generalizable platform for interrogating target- and signal-specific consequences of electrophilic modifications in redox-dependent cell signaling
Lin, Hong-Yu,Haegele, Joseph A.,Disare, Michael T.,Lin, Qishan,Aye, Yimon
supporting information, p. 6232 - 6244 (2015/06/02)
Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized "electrophile toolbox" with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology, T-REX (targetable reactive electrophiles and oxidants), is established by (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept, which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein, one of several redox-sensitive regulators of the Nrf2-ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2-ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background.
2-AMINOMETHYLALKYNYLALKYL-1,3-DITHIANE DERIVATIVES
-
, (2008/06/13)
-