Fmoc solid phase synthesis of serine phosphopeptides via selective protection of serine and on resin phosphorylation

Phosphopeptide Prodrug Bearing an S-Acyl-2-thioethyl Enzyme-Labile Phosphate Protection

“…Synthesis. Currently, two principal strategies are commonly used for the chemical synthesis of phosphorylated peptides: (a) the building-block strategy − where a protected phosphoamino acid is used during stepwise peptide assembly, and (b) the post-assembly method − where the phosphate group is added after peptide chain assembly. This latter approach is referred to a global phosphorylation.…”

Phosphopeptides - Chemical Synthesis, Analysis, Outlook and Limitations.

“…The serine residue to be phosphorylated was protected with a tert-butyldimethylsilyl group in the Fmoc-based solidphase method of Shapiro et al [92]. The advantages of this strategy are that competing O-acylation of serine during chain elongation is avoided, and that the tert-butyldimethylsilyl group can be selectively removed from the resinbound peptide.…”

A practical dealkylation procedure for O,O-dimethyl-phosphotyrosyl-containing peptide-resins

“…Each coupling cycle was followed by an endcapping step with acetic anhydride/pyridine in DMA (1:1:8, v/v/v) in order to prevent the occurrence of deletion sequences. Side chain protection of N%Fmoc amino acids was as follows: tert-butyl for Glu; trityl (Trt) for His and Asn, 2,2,5,7, for Arg; and Boc for Trp.…”

“…Two main strategies can be distinguished for the incorporation of phosphotyrosine into peptide sequences. The first is the postassembly phosphorylation approach [5], where the phosphate group is introduced globally on free hydroxyl groups of the complete peptide sequence by using the dibenzylphosphochloridate [5k] or the phosphoramidite method. Incomplete phosphitylation [6] as well as side product formation during the subsequent oxidation step [5d,g,7] are the major limitations of this method.…”