Combined Fmoc-Alloc strategy for a general SPPS of phosphoserine peptides; preparation of phosphorylation-dependent tau antisera.
A block method for the solid phase synthesis (SPPS) of serine phosphopeptides has been developed using a combination of Fmoc and Alloc strategies. Alloc-Ser[PO(OCH2CH CH2)2] OH2, prepared in a one pot procedure from Alloc-Ser-OH, was introduced at the N-terminus of a sequence prepared by standard Fmoc-SPPS. Global cleavage of the allyl ester based protecting groups, followed by coupling of a tripeptide fragment, led to the tau phosphopeptide, 1. Using tau phosphopeptides a series of phosphorylation state-dependent antisera to human tau protein have been raised. These antisera are valuable tools for studying the tau protein which is found in an abnormal, hyperphosphorylated form in Alzheimer's disease brain.
Shapiro
G
G
Preclinical Research, Sandoz Pharma Ltd, Basel, Switzerland.
Büchler
D
D
Dalvit
C
C
Frey
P
P
Fernández
M C
MC
Gomez-Lor
B
B
Pombo-Villar
E
E
Stauss
U
U
Swoboda
R
R
Waridel
C
C
D000595:Amino Acid Sequence; D000917:Antibody Formation; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007106:Immune Sera / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010766:Phosphorylation; D012694:Serine / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D016875:tau Proteins / Q000276:immunology*
D007106:Immune Sera; D010748:Phosphopeptides; D016875:tau Proteins; D012694:Serine