1207193-13-2Relevant academic research and scientific papers
'Sulfo-click' for ligation as well as for site-specific conjugation with peptides, fluorophores, and metal chelators
Rijkers, Dirk T. S.,Merkx, Remco,Yim, Cheng-Bin,Brouwer, Arwin J.,Liskamp, Rob M. J.
, p. 1 - 5 (2010)
The 'sulfo-click' reaction, which is a chemoselective amidation reaction involving the reaction of an aminoethane sulfonyl azide with a thio acid, encompasses a new approach for ligation and conjugation. Detailed protocols are provided for decorating biol
Synthesis of DOTA-conjugated multimeric [Tyr3]octreotide peptides via a combination of Cu(I)-Catalyzed Click cycloaddition and thio acid/Sulfonyl azide Sulfo-Click amidation and their in vivo evaluation
Yim, Cheng-Bin,Dijkgraaf, Ingrid,Merkx, Remco,Versluis, Cees,Eek, Annemarie,Mulder, Gwenn E.,Rijkers, Dirk T. S.,Boerman, Otto C.,Liskamp, Rob M. J.
experimental part, p. 3944 - 3953 (2010/08/19)
Herein, we describe the design, synthesis, and biological evaluation of a series of DOTA-conjugated monomeric, dimeric, and tetrameric [Tyr 3]octreotide-based analogues as a tool for tumor imaging and/or radionuclide therapy. These compounds were synthesized using a Cu(I)-catalyzed 1,3-dipolar cycloaddition (click reaction) between peptidic azides and dendrimer-derived alkynes and a subsequent metal-free introduction of DOTA via the thio acid/sulfonyl azide amidation (sulfo-click reaction). In a competitive binding assay using rat pancreatic AR42J tumor cells, the monomeric [Tyr 3]octreotide conjugate displayed the highest binding affinity (IC50 = 1.32 nM) followed by dimeric [Tyr3]octreotide (2.45 nM), [DOTA0,Tyr3]octreotide (2.45 nM), and tetrameric [Tyr3]octreotide (14.0 nM). Biodistribution studies with BALB/c nude mice with subcutaneous AR42J tumors showed that the 111In-labeled monomeric [Tyr3]octreotide conjugate had the highest tumor uptake (42.3 ± 2.8 %ID/g) at 2 h p.i., which was better than [111In-DOTA0,Tyr3]octreotide (19.5 ± 4.8 %ID/g). The 111In-labeled dimeric [Tyr 3]octreotide conjugate showed a long tumor retention (25.3 ± 5.9 %ID/g at 2 h p.i. and 12.1 ± 1.3 %ID/g at 24 h p.i.). These promising results can be exploited for therapeutic applications.
