Synthesis and binding selectivity of 7- and 15-decylbenzolactone-V8 for the C1 domains of protein kinase C isozymes.
Benzolactone-V8 (4) is a lactone analogue of the artificial tumor promoter benzolactam-V8 (1). To investigate the effect of hydrophobic substituents at positions 7 and 15 of 4 on binding selectivity for protein kinase C (PKC) isozymes, 7- and 15-decylbenzolactone-V8 (7, 8) were synthesized and their binding affinities for synthetic PKC isozyme C1 peptides were examined. Compound 8 showed moderate selectivity for novel PKC isozymes similar to 9-decylbenzolactone-V8 (5), while 7 was less selective. Compounds 7 and 8 showed no significant selectivity among novel PKC isozymes unlike 8-decylbenzolactone-V8 (6). These results indicate that the introduction of a hydrophobic substituent at position 8 of 4 is most effective in the development of PKC epsilon- and PKCeta-selective binders.
Nakagawa
Yu
Y
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
Irie
Kazuhiro
K
Yamanaka
Nobuhiro
N
Ohigashi
Hajime
H
Tsuda
Ken-ichiro
K
D000818:Animals; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D007769:Lactams / Q000138:chemical synthesis / Q000378:metabolism; D007783:Lactones / Q000138:chemical synthesis* / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D007527:Isoenzymes; D007769:Lactams; D007783:Lactones; C113786:benzolactam V8-310; D011493:Protein Kinase C