ATP-conjugated peptide inhibitors for calmodulin-dependent protein kinase II.
Substrate analog peptides of CaMKII with varying degrees of the inhibitory potency were linked to ATPgammaS either by considering a phosphoryl transfer mechanism or simply by using a relatively long flexible linker. The latter bisubstrate inhibitors showed relatively little effects while the former ones improved inhibitory potency to different levels depending on the binding affinities of the peptide moieties. One of the mechanism-based bisubstrate inhibitors was then utilized to demonstrate an ATP-competitive but peptide substrate-uncompetitive inhibition, supporting an ordered binding mechanism for CaMKII.
Ahn
Dae-Ro
DR
Life Sciences Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Han
Ki-Cheol
KC
Kwon
Hyuk Sung
HS
Yang
Eun Gyeong
EG
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000595:Amino Acid Sequence; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013379:Substrate Specificity
C519001:AIP-1-PEO3-ATP; C519002:AIP-2-PEO3-ATP; C519003:AIP-3-PEO3-ATP; D010455:Peptides; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases