Cell Surface Engineering by a Modified Staudinger Reaction

TLDR

Selective chemical reactions inside cells can elucidate biology or engineer novel interactions. The study presents a chemical transformation that enables selective covalent adduct formation among richly functionalized biopolymers within a cellular context. Using a Staudinger‑type ligation, an azide on cell‑surface glycoconjugates reacts with a biotinylated triarylphosphine to form a stable amide bond, with both partners being abiotic and orthogonal to native cellular components. The transformation’s high selectivity should allow it to operate inside cells, opening new avenues for probing intracellular interactions.

Abstract

Selective chemical reactions enacted within a cellular environment can be powerful tools for elucidating biological processes or engineering novel interactions. A chemical transformation that permits the selective formation of covalent adducts among richly functionalized biopolymers within a cellular context is presented. A ligation modeled after the Staudinger reaction forms an amide bond by coupling of an azide and a specifically engineered triarylphosphine. Both reactive partners are abiotic and chemically orthogonal to native cellular components. Azides installed within cell surface glycoconjugates by metabolism of a synthetic azidosugar were reacted with a biotinylated triarylphosphine to produce stable cell-surface adducts. The tremendous selectivity of the transformation should permit its execution within a cell's interior, offering new possibilities for probing intracellular interactions.