TY - JOUR
T1 - Design, synthesis, and structure-activity relationship of new isobenzofuranone ligands of protein kinase C
AU - Baba, Yoshiyasu
AU - Ogoshi, Yosuke
AU - Hirai, Go
AU - Yanagisawa, Takeshi
AU - Nagamatsu, Kumiko
AU - Mayumi, Satoshi
AU - Hashimoto, Yuichi
AU - Sodeoka, Mikiko
N1 - Funding Information:
We thank Mr. Yasuharu Ijuin (Sagami Chemical Research Center) for X-ray analysis. This work was supported in part by grants from Uehara Memorial Foundation and Hoh-ansha Foundation, Kanagawa Academy of Science and Technology Research Grants, a Grant-in-Aid for Creative Scientific Research (no 13NP0401) and a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, and a Grant-in-Aid for the COE project, Giant Molecules and Complex Systems, from The Ministry of Education, Culture, Sports, Science and Technology.
PY - 2004/6/7
Y1 - 2004/6/7
N2 - 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 PKCδ C1B ligand-binding domain. Several isobenzofuranone derivatives were synthesized and their PKCα binding activities were evaluated. The pivaloyl derivative 1f was found to be a strong PKCα ligand, and the structure-activity relationship is well explained by our proposed binding model.
AB - 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 PKCδ C1B ligand-binding domain. Several isobenzofuranone derivatives were synthesized and their PKCα binding activities were evaluated. The pivaloyl derivative 1f was found to be a strong PKCα ligand, and the structure-activity relationship is well explained by our proposed binding model.
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U2 - 10.1016/j.bmcl.2004.02.097
DO - 10.1016/j.bmcl.2004.02.097
M3 - Article
C2 - 15125969
AN - SCOPUS:2342518915
VL - 14
SP - 2963
EP - 2967
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 11
ER -