title: Design, synthesis, and structure-activity relationship of new isobenzofuranone ligands of protein kinase C.
abstract: Protein kinase C (PKC) is a family of enzymes, which play important roles in intracellular signal transduction. We have designed novel PKC ligands having an isobenzofuranone template, based on the proposed interaction of DAG (1,2-diacyl-sn-glycerol) with the PKCdelta C1B ligand-binding domain. Several isobenzofuranone derivatives were synthesized and their PKCalpha binding activities were evaluated. The pivaloyl derivative 1f was found to be a strong PKCalpha ligand, and the structure-activity relationship is well explained by our proposed binding model.
authors.affiliation: Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba, Sendai, Miyagi 980-8577, Japan.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Baba
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ogoshi
authors.forename: Go
authors.initials: G
authors.lastname: Hirai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yanagisawa
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nagamatsu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mayumi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Mikiko
authors.initials: M
authors.lastname: Sodeoka
mesh_terms: D001572:Benzofurans / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D015394:Molecular Structure; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D001572:Benzofurans; D004791:Enzyme Inhibitors; D008024:Ligands; D011493:Protein Kinase C