Cell Surface Engineering/chemoselective Ligation Reaction

University of California System: University of California, Berkeley
posted on 05/28/2009

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Also see: E. Saxon and C. R. Bertozzi, Cell Surface Engineering By A Modified Staudinger Reaction, Science 2000 Mar. 17: 287 (5460): 2007-2010.

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 model 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 the 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 interaction.

Scientists at UC Berkeley have developed a novel chemoselective ligation reaction that functions in aqueous solution in addition to organic solvents. The reaction is useful in bioconjugation, polymer and material chemistry, and is a powerful tool for gaining insights into biological processes, exploring therapeutic strategies, designing synthetic model surfaces and novel materials for biomedical application. The new reaction offers several unique advantages, including:

Chemoselective ligation reaction can be used as a powerful tool for:
Gaining insights into biological processes: Probing intracellular interactions. Delivery of detectable labels, and receptor ligands for binding by a target receptor. Provides ways of engineering receptors for viral mediated gene transfer. Synthesis of peptides and other polymers.
Exploring therapeutic strategies: Engineered compounds that can provide for pharmacological activity, or can serve as a target for delivery of other molecules. Provides new ways of labeling cells as targets for cancer therapy.
Designing synthetic model surfaces and unique materials for biomedical applications: Provides new ways of adhering cells to nonbiological materials, e.g., medical implants.

The reaction can be used to engineer the composition of cell surfaces, as well as cells’ interior.
Ligations can be performed in aqueous solution under physiological conditions.
Unique properties of the reactive partners (abiotic and chemically orthogonal) provide for extreme selectivity of the reaction