Inhibition of calmodulin-dependent protein kinase II by cyclic and linear peptide alkaloids from Zizyphus species.
The effects of sedative peptide alkaloids from Zizyphus species on calmodulin- dependent protein kinase II were investigated. Protein kinase II activity was assayed on the basis of its ability to activate tryptophan 5-monooxygenase as its substrate in the presence of calmodulin. All thirteen alkaloids tested were stronger inhibitors than chlorpromazine (IC50, 98 microM) on calmodulin-dependent protein kinase II. Among them, the most potent inhibitor was daechuine S27 (IC50 2.95 microM), which was stronger than pimozide (IC50, 15.0 microM).
Han
Yong Nam
YN
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 110-460, Korea. snake@snu.ac.kr
Hwang
Keum Hee
KH
Han
Byung Hoon
BH
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000201:enzymology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D031957:Ziziphus / Q000737:chemistry*
D000470:Alkaloids; D010455:Peptides; D014365:Tryptophan Hydroxylase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases