Synthesis of Suitably Protected Hydroxymethylene Phosphonate- and ‘Phosphate Phosphonate’-Analogues of Phosphoserine and their Incorporation into Synthetic Peptides

Two suitably protected derivatives of phosphoserine 1 have been prepared in which the regular ester-oxygen is replaced by either a hydroxymethylene moiety or by a phosphorylated hydroxymethylene moiety. The second derivative termed ‘phosphate phosphonate’ 3 yields the hydroxymethylene phosphonate 2 upon enzymatic cleavage of the phosphate. Two peptide sequences containing regular phosphoserine or the new derivatives have been prepared by Fmoc solid phase strategy and were investigated for their potential as substrates or inhibitors of alkaline phosphatase. The peptides should be useful tools for investigations with protein phosphatases and protein kinases.