A new type of non-ionic nucleotide analogue with a doubly modified internucleotide linkage, P-boranomethylphosphonate, has been successfully synthesized and characterized. Dithymidine boranomethylphosphonate 5 is the first example of a P-boranomethylphosphonate compound; it is a highly lipophilic phosphodiester analog, which is almost totally resistant to both snake venom phosphodiesterase (SVPDE) and bovine spleen phosphodiesterase (BSPDE). P-boranomethylphosphonates are expected to be promising candidates for mechanistic, diagnostic and therapeutic applications.