ITAM-derived phosphopeptide-containing dendrimers as multivalent ligands for Syk tandem SH2 domain

Kuil, J., Branderhorst, H.M., Pieters, R.J., de Mol, N.J. and Liskamp, R.M.J. (2009) ITAM-derived phosphopeptide-containing dendrimers as multivalent ligands for Syk tandem SH2 domain. Organic and Biomolecular Chemistry, 7(19), pp. 4088-4094. (doi:10.1039/b905938e)

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Abstract

Spleen tyrosine kinase (Syk) is activated when its tandem SH2 domain (tSH2) binds to a diphosphorylated ITAM motif of e.g. the FcεRI receptor. In this divalent interaction each SH2 domain binds to a phosphotyrosine-containing tetrapeptide motif in ITAM. One of those tetrapeptide sequences was synthesized and conjugated to dendrimers via‘click’ chemistry to create a series of functional phosphopeptide-containing dendrimers ranging from a monovalent to an octavalent dendrimer. The affinity of the functionalized dendrimers for Syk tSH2 has been assayed in SPR competition experiments. Both the tetra- and octavalent dendrimer had an affinity in the high nanomolar range, which is approximately 100-fold enhanced compared to the monovalent tetrapeptide, indicating a multivalency effect.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liskamp, Professor Robert
Authors: Kuil, J., Branderhorst, H.M., Pieters, R.J., de Mol, N.J., and Liskamp, R.M.J.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Organic and Biomolecular Chemistry
Publisher:Royal Society of Chemistry
ISSN:1477-0520

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