Cu(i)-assisted click chemistry strategy for conjugation of non-protected cross-bridged macrocyclic chelators to tumour-targeting peptides

Abstract

Copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) click chemistry has inherent challenges for copper-labeled radiopharmaceuticals. An azide-modified phosphonate-based cross-bridged macrocyclic chelator was synthesized for click chemistry conjugation with azide-modified Y3-TATE (a somatostatin analogue) on resin, without the need for protecting the chelator. The ⁶⁴Cu-labeled bioconjugate shows favourable in vitro and in vivo behaviour.