New N-2-labelled fluorescent derivatives of guanosine nucleotides and their interaction with GTP-binding proteins

Convenient syntheses of new fluorescent derivatives of guanosine nucleotide s are described. The analogs bear a fluorescent group attached by an alipha tic linker containing 2 or 4 methylene groups on the N-2 position of the gu anine base. They interact with the small GTPases H-Ras and cdc42 with an ac companying increase in fluorescence yield and display kinetic constants whi ch are similar to those of unmodified nucleotides. The derivatives thus app ear to be attractive alternatives to the widely used 2'(3')-O-methylanthran iloyl derivatives and are likely to be useful for GTPases which do not tole rate modifications of the sugar moiety of the nucleoside.