A Dual-Purpose Non-Canonical Amino Acid for the Expanded Genetic Code: Combining Metal-Binding and Click Chemistry.

ABSTRACT: A rationally designed dual-purpose non-canonical amino acid (Trz) has been synthesised and successfully incorporated into a protein scaffold by genetic code expansion. Trz contains a 5-pyridyl-1,2,4-triazine system, which allows for inverse-electron-demand Diels-Alder (IEDDA) reactions to occur on the triazine ring and for metal ions to be chelated both before and after the click reaction. Trz was successfully incorporated into a protein scaffold and the IEDDA utility of Trz demonstrated through the site-specific labelling of the purified protein with a bicyclononyne. Additionally, Trz was shown to successfully coordinate a cyclometallated iridium(III) centre, providing access to a bioorthogonal luminogenic probe. The luminescent properties of the Ir(III)-bound protein blue-shift upon IEDD

SUBMITTER: Day GJ 

PROVIDER: S-EPMC11656133 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature