Tunable, biodegradable grafting-from glycopolypeptide bottlebrush polymers

Abstract

The cellular glycocalyx and extracellular matrix are rich in glycoproteins and proteoglycans that play essential physical and biochemical roles in all life. Synthetic mimics of these natural bottlebrush polymers have wide applications in biomedicine, yet preparation has been challenged by their high grafting and glycosylation densities. Using one-pot dual-catalysis polymerization of glycan-bearing α-amino acid N-carboxyanhydrides, we report grafting-from glycopolypeptide brushes. The materials are chemically and conformationally tunable where backbone and sidechain lengths were precisely altered, grafting density modulated up to 100%, and glycan density and identity tuned by monomer feed ratios. The glycobrushes are composed entirely of sugars and amino acids, are non-toxic to cells, and are degradable by natural proteases. Inspired by native lipid-anchored proteoglycans, cholesterol-modified glycobrushes were displayed on the surface of live human cells. Our materials overcome long-standing challenges in glycobrush polymer synthesis and offer new opportunities to examine glycan presentation and multivalency from chemically defined scaffolds.

Biomimetic Glycosylated Polythreonines by N-Carboxyanhydride Polymerization

“…NCA-derived polypeptides are widely used as commodity chemicals and as biomaterials for applications from tissue engineering and drug delivery to biomineralization and nanoelectronics . In our own work, NCA chemistry has been used to prepare synthetic mimics of the natural glycoproteins mucins. − Mucins are the primary protein component of mucus and are involved in epithelial hydration, lubrication, and defense …”

Polymers Inspired by Heparin and Heparan Sulfate for Viral Targeting

“… 221 , 222 Here, synthetic glycocalyx building blocks equipped with a membrane anchor, for example, a cholesterol unit, are inserted into a live cell surface, thereby artificially altering or reconstituting the cell’s glycocalyx ( Figure 7 A). 223 Through this method, polymeric sGAG mimetics have successfully been used to derive new insights into the functional role of such carbohydrates within the complex environment of the cell surface. 224 − 230 For example, the Hsieh-Wilson lab used CS to engineer the cell surface of neurons and could show increased activation of neurotrophin-mediated signaling pathways and enhanced axonal growth in dependence of the sulfation pattern installed through the choice of polysaccharide ( Figure 7 B).…”

“…This presentation and localization thus offer several additional levels of structural control and spatial organization that need to be considered when trying to understand or manipulate phenomena, such as HSPG-mediated viral attachment. Indeed, glycocalyx engineering now enables researchers to tune selected components of the glycocalyx, for example, by enzymatic treatment or glycan labeling, and study the effects, not at the level of the single molecule but on the larger ensemble. , Recently, the so-called de novo glycocalyx engineering has gained increasing attention. , Here, synthetic glycocalyx building blocks equipped with a membrane anchor, for example, a cholesterol unit, are inserted into a live cell surface, thereby artificially altering or reconstituting the cell’s glycocalyx (Figure A) . Through this method, polymeric sGAG mimetics have successfully been used to derive new insights into the functional role of such carbohydrates within the complex environment of the cell surface. − For example, the Hsieh-Wilson lab used CS to engineer the cell surface of neurons and could show increased activation of neurotrophin-mediated signaling pathways and enhanced axonal growth in dependence of the sulfation pattern installed through the choice of polysaccharide (Figure B) .…”

Bottlebrush inspired injectable hydrogel for rapid prevention of postoperative and recurrent adhesion

“…Recently, antifouling bottle-brush polymers have been extensively developed for the antifouling coating of in vivo implanted devices [ [14] , [15] , [16] ]. Among these, ultra-hydrophilic bottlebrush polymers have demonstrated excellent antifouling capability for non-specific proteins, bacteria, or fibroblasts [ 17 , 18 ].…”