Chemical Remodeling of Cell‐Surface Sialic Acids through a Palladium‐Triggered Bioorthogonal Elimination Reaction

Abstract

We herein report a chemical decaging strategy for the in situ generation of neuramic acid (Neu), a unique type of sialic acid, on live cells by the use of a palladium-mediated bioorthogonal elimination reaction. Palladium nanoparticles (Pd NPs) were found to be a highly efficient and biocompatible depropargylation catalyst for the direct conversion of metabolically incorporated N-(propargyloxycarbonyl)neuramic acid (Neu5Proc) into Neu on cell-surface glycans. This conversion chemically mimics the enzymatic de-N-acetylation of N-acetylneuramic acid (Neu5Ac), a proposed mechanism for the natural occurrence of Neu on cell-surface glycans. The bioorthogonal elimination was also exploited for the manipulation of cell-surface charge by unmasking the free amine at C5 to neutralize the negatively charged carboxyl group at C1 of sialic acids.

Dissociative Bioorthogonal Reactions

“…Metallic Pd nanoparticles can also remove proc groups . These nanoparticles effectively deprotected proc‐protected aminocoumarin, achieving 95 % conversion within minutes in HEPES/DMSO (95:5) with stoichiometric Pd 0 .…”

“…Wang et al. further used dissociative bioorthogonal chemistry to manipulate the charge on cell‐surface glycans to control cell clustering …”

Chemical and Enzymatic Strategies for Bacterial and Mammalian Cell Surface Engineering

“…The propargyloxycarbonyl group of the alkyne‐functionalized neuramic acid (Neu), which was incorporated into the surface glycans of the cells via metabolic glycan engineering, could be efficiently removed by palladium nanoparticles (Pd NPs) to produce Neu in situ on live cells. This two‐step approach provides a simple tool to investigate the biological function of Neu . Overall, without complicated genetic engineering of the cells, by just relying on the tolerance of the native biosynthesis machinery, cell surface features can be tailored using diverse chemical transformations.…”

Bioorthogonal Uncaging of the Active Metabolite of Irinotecan by Palladium‐Functionalized Microdevices

“…Palladium (Pd) catalysts are one of the tools of choice currently under investigation to release caged drugs in vitro and in vivo . The selection of this metal is based on its high bio‐compatibility, its versatility to adopt different shapes and sizes and its remarkable capabilities to catalyze N ‐ and O ‐dealkylation reactions on manifold types of substrates under physiological conditions . Our lab is currently investigating the application of heterogeneous Pd catalysts as implantable devices to mediate drug release with spatiotemporal control and in a catalytic fashion, with the goal of improving the safety profile of chemotherapies without having the short, limited life of other local therapy modalities such as drug eluting devices (carmustine wafers) or brachytherapy …”