1.D.62 The Bis-Triazolyl DiGuanosine Derivative Channel-forming (TDG) Family
Detailed procedures for the synthesis and ion-channel activity measurements of four diguanosine derivatives, each made up of two guanosine moieties separated by a covalent linker (e.g., PEG) have been reported (Kumar et al. 2016). The procedure requires the preparation of guanosine azide and guanosine alkine building blocks, as well as the preparation of four distinct synthetic linkers, each containing either two alkynes or two azides. The diguanosine derivatives were synthesized using a 'one-pot' modular synthetic approach based on Cu(I)-catalyzed azide and alkyne cycloaddition. The ion-channel activity of these diguanosine derivatives for the transport of ions across phospholipid bilayers was investigated using voltage-clamp experiments. Ion-channel activities in the presence of different cations (e.g., Na+, K+ and Cs+) and the inhibition of the activities using the nucleobase cytosine were characterized (Kumar et al. 2016).