897398-24-2Relevant academic research and scientific papers
α-Arylidene Diacylglycerol-Lactones (DAG-Lactones) as Selective Ras Guanine-Releasing Protein 3 (RasGRP3) Ligands
Ann, Jihyae,Czikora, Agnes,Saini, Amandeep S.,Zhou, Xiaoling,Mitchell, Gary A.,Lewin, Nancy E.,Peach, Megan L.,Blumberg, Peter M.,Lee, Jeewoo
, p. 6261 - 6276 (2018/06/11)
Diacylglycerol-lactones have proven to be a powerful template for the design of potent ligands targeting C1 domains, the recognition motif for the cellular second messenger diacylglycerol. A major objective has been to better understand the structure activity relations distinguishing the seven families of signaling proteins that contain such domains, of which the protein kinase C (PKC) and RasGRP families are of particular interest. Here, we synthesize a series of aryl- and alkyl-substituted diacylglycerol-lactones and probe their relative selectivities for RasGRP3 versus PKC. Compound 96 showed 73-fold selectivity relative to PKCα and 45-fold selectivity relative to PKC? for in vitro binding activity. Likewise, in intact cells, compound 96 induced Ras activation, a downstream response to RasGRP stimulation, with 8-29 fold selectivity relative to PKCδ S299 phosphorylation, a measure of PKCδ stimulation.
Conformationally constrained analogues of diacylglycerol. 26. Exploring the chemical space surrounding the C1 domain of protein kinase C with DAG-lactones containing aryl groups at the sn-1 and sn-2 positions
Kang, Ji-Hye,Benzaria, Samira,Sigano, Dina M.,Lewin, Nancy E.,Pu, Yongmei,Peach, Megan L.,Blumberg, Peter M.,Marquez, Victor E.
, p. 3185 - 3203 (2007/10/03)
Diacylglycerol lactones (DAG-lactones) are known to operate as effective agonists of protein kinase C (PKC), surpassing in potency the activity of natural diacylglycerol (DAG). Localization of activated PKC isozymes in the cell is determined in part by th
