Versatile conjugation of octreotide to dendrimers by cycloaddition (“click”) chemistry to yield high-affinity multivalent cyclic peptide dendrimers

Yim, C.-B., Boerman, O.C., de Visser, M., de Jong, M., Dechesne, A.C., Rijkers, D.T.S. and Liskamp, R.M.J. (2009) Versatile conjugation of octreotide to dendrimers by cycloaddition (“click”) chemistry to yield high-affinity multivalent cyclic peptide dendrimers. Bioconjugate Chemistry, 20(7), pp. 1323-1331. (doi:10.1021/bc900052n)

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Abstract

The somatostatin analogue Tyr3-octreotide, which has a high binding affinity for the SSTR2 receptor (somatostatin receptor subtype 2) expressed on tumor cells, is used clinically for the diagnosis and treatment of a variety of neuroendocrine tumors and gastrointestinal disorders. There is growing interest in the development of multivalent peptide systems, because they may have enhanced binding affinity compared to monovalent analogues. In this report, we describe the design and synthesis of a series of Tyr3-octreotide-containing monomeric, dimeric, and tetrameric dendrimeric conjugates. These multivalent dendrimeric cyclic peptides were obtained using Cu(I)-catalyzed 1,3-dipolar cycloaddition between peptidyl azides and dendrimeric alkynes. Their affinities for the SSTR2 receptor were determined by a competitive binding assay on rat brain sections.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liskamp, Professor Robert
Authors: Yim, C.-B., Boerman, O.C., de Visser, M., de Jong, M., Dechesne, A.C., Rijkers, D.T.S., and Liskamp, R.M.J.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Bioconjugate Chemistry
ISSN:1043-1802
ISSN (Online):1520-4812

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