Site-Selective and Biocompatible Growth of Polymers from Glycan Moieties of Glycoproteins and Living Cells

Abstract

Formation of protein–polymer conjugates (PPCs) is critical for many studies in chemical biology, biomedicine, and enzymatic catalysis. Polymers with coordinated physicochemical properties confer synergistic functions to PPCs that overcome the inherent limitation of proteins. However, application of PPCs has been synthetically restricted by the limited modification sites and polymer grafting method. Here, we present a versatile strategy for site-selective PPC synthesis. The initiator was specifically tethered to the preoxidized glycan moieties through oxime chemistry. Polymer brushes were grown in situ from the glycan by atom-transfer radical polymerization to generate well-controlled PPCs. Notably, the modification is site-specific, multivalent, and alterable depending on protein glycosylation. Additionally, we demonstrated that the cytocompatible method enabled the growth of polymer chains from the surface of living yeast cells. These results verified a facile technology for surface modification of biomacromolecules by desired polymers for various biomedical applications.

Unimolecular Cascaded Multienzyme Conjugates Modulate the Microenvironment of Diabetic Wound to Promote Healing

“…Site-specific conjugation of the polymer to protein generally involves additional preprocessing steps and a limited amount of grafting. To overcome these shortcomings, we have reported a versatile approach to overcome these shortcomings through the multivalent conjugation of polymers to the glycan moieties of glycoproteins. , Briefly, this approach begins with gently oxidizing glycans on GOx with sodium periodate to produce ketones (GOx-Oxi) on the glycan moieties . The initiator ABM specifically reacted with the ketones to form a macroinitiator (GOx-ABM).…”

“…Poly(N-acryloyl-lysine) (pLAAm) was synthesized according to S. Nagaoka's work 40 (Figures S1 and S2). (2-(Aminooxy)ethyl)2-bromo-2-methylpropanoate (ABM) was synthesized as previously reported, 41 and ELISA kits were bought from 4A Biotech. E. coli (K-12 MG16653) and S. aureus (ATCC 45330) were obtained from our laboratory collection.…”

The challenges of controlling polymer synthesis at the molecular and macromolecular level

“…These become apparent when considering the thiocarbonylthio as an electrophilic carbon analogous to a car- American Chemical Society, respectively. [122][123][124] Polymer Chemistry Perspective bonyl, a "dieneophile" available for hetero-[4 + 2] cycloadditions, or as a site for radical chain transfer (Fig. 5A).…”

“…Fig. 4 Highlights of biomolecular conjugation through precise control of end group chemistry, including membrane-bound glycoproteins (A), antibodies (B) and nucleotides (C), adapted with permission from Bi et al Copyright 2021 American Chemical Society, Chou et al Copyright 2018 American Chemical Society and Averick et al Copyright 2012American Chemical Society, respectively [122][123][124]. …”

Plug-and-Play Functionalization of Protein–Polymer Conjugates for Tunable Catalysis Enabled by Genetically Encoded “Click” Chemistry

“…Currently, the major strategies to synthesize protein–polymer conjugates are “grafting to” and “grafting from” methods. , However, the synthesis process often involves chemical modification of proteins (e.g., the introduction of initiators to the protein) and relative harsh chemical reactions for the conjugation (e.g., monomers/polymers, organic solvents, and metal catalysts), unavoidably leading to partial denaturation and decreased activity of the original proteins/enzymes. − Another constraint of the protein–polymer conjugates is that once they are synthesized, their properties are usually fixed due to the selected proteins and polymers, limiting more applications of one conjugate. Therefore, this research field desires a new strategy to address two requirements: (i) maximally retaining protein function/activity during the conjugation using protein-favored mild conditions to tether polymer chains to proteins and (ii) fabricating protein–polymer conjugates as a generic foundation that can be further functionalized for broad applications.…”