Versatile conjugation of octreotide to dendrimers by cycloaddition ("click") chemistry to yield high-affinity...

The somatostatin analogue Tyr(3)-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 Tyr(3)-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.