bond. The method displayed impressive scope for a range of
amino acids at the ligation junction, and, as such, should serve
as a useful tool for the construction of biologically relevant
peptides, phosphopeptides, proteins and phosphoproteins in
future studies. We have conducted preliminary experiments
which suggest that acyl phosphates can undergo rapid acyl
migration to the N-terminal amine of a peptide however, it is
not yet clear that such an intermediate is formed during the
ligation reactions. Further delineation of the mechanism of the
phosphate-assisted ligation will be the focus of future research
in our laboratory. In addition, the phosphate-assisted ligation is
currently being employed in the total synthesis of biologically
relevant phospho- and glycoproteins in our research group.
We thank the Australian Research Council for funding and
the Endeavour Research Fellowship for financial support
(GLT). We would also like to thank Dr Kelvin Picker for
his technical assistance with HPLC and LC-MS analysis.
Notes and references
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Scheme 3 Enzymatic dephosphorylation of ligation products.
The generation of unmodified peptides by enzymatic dephos-
phorylation reactions post-ligation therefore provides a direct
disconnection at serine and threonine residues, a novel addition
to the ligation chemistry toolbox.
In summary, we have developed an efficient new method for
the construction of phosphopeptides and peptides. The reaction
utilises the reactivity of an N-terminal phosphoserine or phospho-
threonine residue to facilitate the formation of a native peptide
ꢁc
This journal is The Royal Society of Chemistry 2009
4262 | Chem. Commun., 2009, 4260–4262