TPDYs: strained macrocyclic diynes for bioconjugation processes

Abstract

A terphenyl diyne (TPDY) macrocycle, 3,5-TPDY, has been developed incorporating a bent 1,3-diyne that is active in SPAAC processes affording atropoisomeric triazole products, as well as cycloadditions with diazoacetates and tetrazines. A pendant amine allowed bioconjugation of TPDY to two proteins in a microbial transglutaminase-catalyzed reaction. In contrast to many cycloalkyne SPAAC reagents, the TPDY stabilization occurs via interactions of π and π* orbitals of the adjacent alkynes.