Modular One-Pot Strategy for the Synthesis of Heterobivalent Tracers
Language
EN
Article de revue
This item was published in
ACS Medicinal Chemistry Letters. 2023-05-11, vol. 14, n° 5, p. 636-644
English Abstract
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, ...Read more >
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 SAr 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 and (receptor binding affinity, biodistribution, imaging) as an illustration that the assembly methodology preserves the tumor targeting properties of the ligands.Read less <
English Keywords
Bioconjugation
Click chemistry
Drug delivery
Heterobivalent ligands
Radiopharmaceuticals
ANR Project
France Life Imaging - ANR-11-INBS-0006