Structural analysis of high affinity divalent phosphopeptide hybrids of spleen tyrosine kinase

Catalina, M.I., Dekker, F.J., Liskamp, R.M.J. , Versluis, C., Maier, C.S. and Heck, A.J.R. (2003) Structural analysis of high affinity divalent phosphopeptide hybrids of spleen tyrosine kinase. International Journal of Mass Spectrometry, 228(2-3), pp. 879-890. (doi: 10.1016/S1387-3806(03)00190-8)

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A set of synthetic phosphorylated peptidomimetic inhibitors of spleen tyrosine kinase (Syk), targeted towards its two tandem Src homology-2 (SH2) domains, was studied by nano-electrospray tandem mass spectrometry in both positive and negative ionisation mode. The design of the peptidomimetic compounds was based on the replacement of the intervening amino acid sequence of a Syk-binding di-phosphopeptide by non-peptide spacers based on either ethylene glycol or amino-propynyl-benzoate. Collision-induced dissociation (CID) spectra of the protonated molecular ions [M+H]+ allowed full characterisation of the peptide hybrids. Preferred cleavage at the amide bond N-terminal to the adjacent polyethylene glycol (PEG) and the propynyl-benzoate (PrB) linkers was observed. In general, it thus appears that preferred sequential amino acid fragmentation takes place from the N-terminus up to the linker molecule followed by subsequent internal fragmentation starting at the C-terminus. Additionally, tandem CID spectra of the doubly de-protonated molecular ions [M–2H]2− of every compound showed the m/z 79/97 phosphate-specific ions plus a remarkably intense ion at m/z 297. The mechanism proposed for the m/z 297-ion occurrence goes through a five-membered ring formation giving an N-terminal pyroGlu structure as derived from MSn spectra.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Liskamp, Professor Robert
Authors: Catalina, M.I., Dekker, F.J., Liskamp, R.M.J., Versluis, C., Maier, C.S., and Heck, A.J.R.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:International Journal of Mass Spectrometry
ISSN (Online):1873-2798

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