Modular One-Pot Strategy for the Synthesis of Heterobivalent Tracers.

Autor: Bailly T; Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR CNRS 6302, Université de Bourgogne, 21000 Dijon, France., Bodin S; University of Bordeaux, CNRS, EPHE, INCIA, UMR 5287, Bordeaux F-33000, France., Goncalves V; Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR CNRS 6302, Université de Bourgogne, 21000 Dijon, France., Denat F; Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR CNRS 6302, Université de Bourgogne, 21000 Dijon, France., Morgat C; University of Bordeaux, CNRS, EPHE, INCIA, UMR 5287, Bordeaux F-33000, France.; Nuclear Medicine Department, University Hospital of Bordeaux, Bordeaux F-33000, France., Prignon A; UMS28 Laboratoire d'Imagerie Moléculaire Positonique (LIMP), Sorbonne Université, Paris 75020, France., Valverde IE; Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR CNRS 6302, Université de Bourgogne, 21000 Dijon, France.
Jazyk: angličtina
Zdroj: ACS medicinal chemistry letters [ACS Med Chem Lett] 2023 Apr 21; Vol. 14 (5), pp. 636-644. Date of Electronic Publication: 2023 Apr 21 (Print Publication: 2023).
DOI: 10.1021/acsmedchemlett.3c00057
Abstrakt: Bivalent ligands, i.e., molecules having two ligands covalently connected by a linker, have been gathering attention since the first description of their pharmacological potential in the early 80s. However, their synthesis, particularly of labeled heterobivalent ligands, can still be cumbersome and time-consuming. We herein report a straightforward procedure for the modular synthesis of labeled heterobivalent ligands (HBLs) using dual reactive 3,6-dichloro-1,2,4,5-tetrazine as a starting material and suitable partners for sequential S N Ar and inverse electron-demand Diels-Alder (IEDDA) reactions. This assembly method conducted in a stepwise or in a sequential one-pot manner provides quick access to multiple HBLs. A conjugate combining ligands toward the prostate-specific membrane antigen (PSMA) and the gastrin-releasing peptide receptor (GRPR) was radiolabeled, and its biological activity was assessed in vitro and in vivo (receptor binding affinity, biodistribution, imaging) as an illustration that the assembly methodology preserves the tumor targeting properties of the ligands.
Competing Interests: The authors declare no competing financial interest.
(© 2023 American Chemical Society.)
Databáze: MEDLINE
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