Synthesis of a triply phosphorylated pentapeptide from human tau-protein.
Two different strategies for the synthesis of a triply phosphorylated pentapeptide are described. In both cases a monophosphorylated selectively N-deprotected tripeptide is employed as C-terminal fragment. Coupling of this building block with a C-terminally unmasked bis-phosphorylated seryl-dipeptide unexpectedly failed due to decomposition of this peptide upon activation with different coupling reagents. Instead stepwise N-terminal elongation of the peptide chain with serine derivatives and subsequent O-phosphorylation of the serine OH-groups was successful. These results indicate that assembly of multiply phosphorylated peptides from preformed multiply phosphorylated phosphopeptide building blocks in general may be problematic and that a stepwise elongation of the amino acid chain may be preferable.
Kuder
N
N
Max-Planck-Institut für Molekulare Physiologie, Abteilung Chemische Biologie, Dortmund, Germany.
Zelinski
T
T
Pathak
T
T
Seitz
O
O
Waldmann
H
H
D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D010446:Peptide Fragments / Q000138:chemical synthesis*; D010748:Phosphopeptides / Q000138:chemical synthesis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D016875:tau Proteins / Q000737:chemistry*
D010446:Peptide Fragments; D010748:Phosphopeptides; D016875:tau Proteins