Intramolecular pyrophosphate formation during N alpha-9-fluorenylmethyloxycarbonyl (Fmoc) solid-phase synthesis of peptides containing adjacent phosphotyrosine residues.
The derivative N alpha-9-fluorenylmethyloxycarbonyl-O-phospho-L-tyrosine [Fmoc-Tyr(PO3H2)-OH] has been used successfully for the solid-phase synthesis of a wide variety of phosphorylated peptides. However, when it is used to incorporate consecutive phosphotyrosine residues, a pyrophosphate linkage can form between the two adjacent tyrosines. Incorporation of unprotected phosphotyrosine during the synthesis of peptides with multiple phosphotyrosine residues has been studied as a function of coupling conditions and the absence or presence of intervening amino acid residues. The pyrophosphate-forming side reaction is more severe with increased coupling times and/or repetitions of coupling and occurs only when the phosphotyrosine residues are directly adjacent to one another.
Ottinger
E A
EA
Department of Chemistry, University of Minnesota, Minneapolis 55455, USA.
Xu
Q
Q
Barany
G
G
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D005449:Fluorenes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010755:Organophosphates / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D019000:Phosphotyrosine / Q000737:chemistry*
D005449:Fluorenes; D010755:Organophosphates; D010455:Peptides; D019000:Phosphotyrosine