Indolactam-V is involved in the CH/pi interaction with Pro-11 of the PKCdelta C1B domain: application for the structural optimization of the PKCdelta ligand.
The CH/pi interaction between the indole ring of indolactam-V (IL-V) and the hydrogen atom at position 4 of Pro-11 of the PKCdelta C1B domain was evaluated using the mutant peptide of the PKCdelta C1B domain, in which the CH/pi interaction was inhibited by substitution of the hydrogen atom with a fluorine atom. IL-V showed about a 10 times lower binding affinity to the mutant peptide compared to the wild-type peptide, suggesting that the CH/pi interaction could play a pivotal role in the binding of IL-V to the PKCdelta C1B domain. On the other hand, benzolactam-V8 (BL-V8), with the benzene ring instead of the indole ring of IL-V, might lack the CH/pi interaction. The low binding affinity of BL-V8 could be enhanced by the effective formation of the CH/pi interaction as exemplified by the synthesis of naphtholactam-V8 (NL-V8).
Nakagawa
Yu
Y
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
Irie
Kazuhiro
K
Yanagita
Ryo C
RC
Ohigashi
Hajime
H
Tsuda
Ken-Ichiro
K
D001665:Binding Sites; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D007769:Lactams / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D011392:Proline / Q000737:chemistry / Q000378:metabolism; D011493:Protein Kinase C / Q000737:chemistry* / Q000378:metabolism; D051745:Protein Kinase C-delta
D007211:Indoles; D007769:Lactams; D008024:Ligands; C043969:indolactam V; D011392:Proline; D011493:Protein Kinase C; D051745:Protein Kinase C-delta