Convenient preparation of phosphopeptide fragments using High TFMSA system and its application to synthesis of long chain phosphopeptides

Protein phosphorylation provides structural and functional changes for proteins involved in intracellular signal transduction pathways [1]. Due to the important role of phosphorylation/dephosphorylation in biology, long chain phosphopeptides have received much attention as useful biological and biochemical tools to elucidate various cellular processes including signal transduction. Previously we reported a efficient synthetic methodology for phosphopeptides [2, 3]. In the present study, we tried to develop a new synthetic methodology for long chain phosphopeptides and found that partially protected phosphopeptide fragments [ClZ(2-chlorobenzyloxycarbonyl) group for lysine and methyl groups for phosphoamino acids] can be obtained by treatment of protected peptidyl resins with High TFMSA system with efficient cleavage and removal of the other protecting groups. This finding prompted us to apply the High TFMSA system to the preparations of the useful partially protected phosphopeptide fragments as the building blocks in thioester fragment condensation strategy [4]. Here, we report the convenient synthetic method of phosphopeptide fragments using High TFMSA system.