Application of Metal‐Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates
- 11 July 2008
- journal article
- research article
- Published by Wiley in ChemBioChem
- Vol. 9 (11) , 1805-1815
- https://doi.org/10.1002/cbic.200800074
Abstract
The tandem 1,3-dipolar cycloaddition-retro-Diels–Alder (tandem crDA) reaction is presented as a versatile method for metal-free chemoselective conjugation of a DTPA radiolabel to N-δ-azido-cyclo(-Arg-Gly-Asp-d-Phe-Orn-) via oxanorbornadiene derivatives. To this end, the behavior of several trifluoromethyl-substituted oxanorbornadiene derivatives in the 1,3-dipolar cycloaddition was studied and optimized to give a clean and efficient method for bio-orthogonal ligation in an aqueous environment. After radioisotope treatment, the resulting 111In-labeled c(RGD)-CF3-triazole-DTPA conjugate was subjected to preliminary biological evaluation and showed high affinity for αvβ3 (IC50=192 nM) and favorable pharmacokinetics.Keywords
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