Liquid-phase synthesis of a pegylated adenosine-oligoarginine conjugate, cell-permeable inhibitor of cAMP-dependent protein kinase.
An adenosine-oligoarginine conjugate (ARC) was assembled in a stepwise manner on a poly(ethylene glycol) carrier. The pegylated conjugate inhibited cAMP-dependent protein kinase with IC(50)=460 nM and the cellular uptake of its BODIPY FL derivative was demonstrated and compared to that of free ARC with fluorescence microscopy.
Viht
Kaido
K
Institute of Organic and Bioorganic Chemistry, University of Tartu, 2 Jakobi St., 51014, Tartu, Estonia.
Padari
Kärt
K
Raidaru
Gerda
G
Subbi
Juhan
J
Tammiste
Indrek
I
Pooga
Margus
M
Uri
Asko
A
D000241:Adenosine / Q000737:chemistry; D002463:Cell Membrane Permeability; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D015195:Drug Design; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013329:Structure-Activity Relationship
D004337:Drug Carriers; D004791:Enzyme Inhibitors; D010455:Peptides; C015462:polyarginine; D011092:Polyethylene Glycols; D017868:Cyclic AMP-Dependent Protein Kinases; D000241:Adenosine