Versatile Conjugation of Octreotide to Dendrimers by Cycloaddition (“Click”) Chemistry to Yield High-Affinity Multivalent Cyclic Peptide Dendrimers

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• 作者：Cheng-Bin Yim ; Otto C. Boerman ; Monique de Visser ; Marion de Jong ; Annemarie C. Dechesne ; Dirk T. S. Rijkers ; Rob M. J. Liskamp
• 刊名：Bioconjugate Chemistry
• 出版年：2009
• 出版时间：July 15, 2009
• 年：2009
• 卷：20
• 期：7
• 页码：1323-1331
• 全文大小：298K
• 年卷期：v.20,no.7(July 15, 2009)
• ISSN：1520-4812

文摘

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.