Synthesis of GTP‐Derived Ras Ligands

A practical and convenient method for the synthesis of acid‐ and base‐sensitive GTP analogues carrying a further substituent at the terminal phosphate has been developed. Key to the successful synthesis of these potential ligands of the Ras protein is the use of Pd 0 ‐sensitive allyl protecting groups in a one‐pot synthesis that avoids evaporation steps. Initial biochemical analysis of a representative compound revealed that such GTP analogues can bind to Ras and might open up the possibility of developing small molecules that can act as deactivators of oncogenic Ras.