INTRAMOLECULAR PYROPHOSPHATE FORMATION DURING N-ALPHA-9-FLUORENYLMETHYLOXYCARBONYL (FMOC) SOLID-PHASE SYNTHESIS OF PEPTIDES CONTAINING ADJACENT PHOSPHOTYROSINE RESIDUES

The derivative 9-fluorenylmethyl-oxycarbonyl-O-phospho-L-tyrosine [Fmo c-Tyr(PO3H2)-OH] has been used successfully for the solid-phase synthe sis of a wide variety of phosphorylated peptides. However when it is u sed to incorporate consecutive phosphotyrosine residues, a pyrophospha te linkage can form between the two adjacent tyrosines. Incorporation of unprotected phosphotyrosine during the synthesis of peptides with m ultiple phosphotyrosine residues has been studied as a function of cou pling conditions and the absence or presence of intervening amino acid residues. The pyrophosphate-forming side reaction is more severe with increased coupling dimes and/or repetitions of coupling and occurs on ly when the phosphotyrosine residues are directly adjacent to one anot her.