Application of Metal-Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates

S.S van Berkel; A.J. Dirks; S.A. Meeuwissen; D.L.L. Pingen; O.C. Boerman; P. Laverman; F.L. van Delft; Jeroen Johannes Lambertus Maria Cornelissen; F.P.J.T. Rutjes

doi:10.1002/cbic.200800074

Application of Metal-Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates

S.S van Berkel, A.J. Dirks, S.A. Meeuwissen, D.L.L. Pingen, O.C. Boerman, P. Laverman, F.L. van Delft, Jeroen Johannes Lambertus Maria Cornelissen, F.P.J.T. Rutjes

Biomolecular Nanotechnology

Research output: Contribution to journal › Article › Academic › peer-review

92 Citations (Scopus)

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.

Original language	Undefined
Pages (from-to)	1805-1815
Journal	ChemBioChem
Volume	9
Issue number	11
DOIs	https://doi.org/10.1002/cbic.200800074
Publication status	Published - 2008

Keywords

METIS-306464

Access to Document

10.1002/cbic.200800074

Cite this

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title = "Application of Metal-Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates",

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.",

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T1 - Application of Metal-Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates

AU - van Berkel, S.S

AU - Dirks, A.J.

AU - Meeuwissen, S.A.

AU - Pingen, D.L.L.

AU - Boerman, O.C.

AU - Laverman, P.

AU - van Delft, F.L.

AU - Cornelissen, Jeroen Johannes Lambertus Maria

AU - Rutjes, F.P.J.T.

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - METIS-306464

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DO - 10.1002/cbic.200800074

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