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

Research output: Contribution to journalArticleAcademicpeer-review

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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 languageUndefined
Pages (from-to)1805-1815
JournalChemBioChem
Volume9
Issue number11
DOIs
Publication statusPublished - 2008

Keywords

  • METIS-306464

Cite this

van Berkel, S. S., Dirks, A. J., Meeuwissen, S. A., Pingen, D. L. L., Boerman, O. C., Laverman, P., ... Rutjes, F. P. J. T. (2008). Application of Metal-Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates. ChemBioChem, 9(11), 1805-1815. https://doi.org/10.1002/cbic.200800074
van Berkel, S.S ; Dirks, A.J. ; Meeuwissen, S.A. ; Pingen, D.L.L. ; Boerman, O.C. ; Laverman, P. ; van Delft, F.L. ; Cornelissen, Jeroen Johannes Lambertus Maria ; Rutjes, F.P.J.T. / Application of Metal-Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates. In: ChemBioChem. 2008 ; Vol. 9, No. 11. pp. 1805-1815.
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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.",
keywords = "METIS-306464",
author = "{van Berkel}, S.S and A.J. Dirks and S.A. Meeuwissen and D.L.L. Pingen and O.C. Boerman and P. Laverman and {van Delft}, F.L. and Cornelissen, {Jeroen Johannes Lambertus Maria} and F.P.J.T. Rutjes",
year = "2008",
doi = "10.1002/cbic.200800074",
language = "Undefined",
volume = "9",
pages = "1805--1815",
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van Berkel, SS, Dirks, AJ, Meeuwissen, SA, Pingen, DLL, Boerman, OC, Laverman, P, van Delft, FL, Cornelissen, JJLM & Rutjes, FPJT 2008, 'Application of Metal-Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates', ChemBioChem, vol. 9, no. 11, pp. 1805-1815. https://doi.org/10.1002/cbic.200800074

Application of Metal-Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates. / van Berkel, S.S; Dirks, A.J.; Meeuwissen, S.A.; Pingen, D.L.L.; Boerman, O.C.; Laverman, P.; van Delft, F.L.; Cornelissen, Jeroen Johannes Lambertus Maria; Rutjes, F.P.J.T.

In: ChemBioChem, Vol. 9, No. 11, 2008, p. 1805-1815.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

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

U2 - 10.1002/cbic.200800074

DO - 10.1002/cbic.200800074

M3 - Article

VL - 9

SP - 1805

EP - 1815

JO - ChemBioChem

JF - ChemBioChem

SN - 1439-4227

IS - 11

ER -

van Berkel SS, Dirks AJ, Meeuwissen SA, Pingen DLL, Boerman OC, Laverman P et al. Application of Metal-Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates. ChemBioChem. 2008;9(11):1805-1815. https://doi.org/10.1002/cbic.200800074