PET-cGMP-8-TMAmd-(PEG pd 2000)-AmdMT-8-cGMP-PET

Polymer-linked dimeric (PLD) cGMP analogue in which two cGMP units are linked by a polydisperse 2000 Dalton spacer on basis of polyethylene glycol (PEG) via thio-functions at the C8 positions. In addition, β-phenyl-1,N2-etheno (PET) groups have been attached to both guanine nucleobases. Membrane-permeant cGMP dimer with enhanced PKG activation properties by addressing two binding sites simultaneously with a single molecule.
Activation constants of PET-cGMP-8-TMAmd-(PEG pd 2000)-AmdMT-8-cGMP-PET in vitro on purified cGMP-dependent protein kinase (PKG) isozymes were measured to be in the range of < 1 nM (PKG1α and PKG1β) and ~80 nM (PKG2), respectively (BIOLOG in-house data). PET-cGMP-8-TMAmd-(PEG pd 2000)-AmdMT-8-cGMP-PET decreased cell viability in the PKG2 expressing colon cancer cell line Caco-2, but not in the PKG2 expressing colon cancer cell lines HCT 116 and HT-29.