Principles of glycocalyx engineering with hydrophobic-anchored synthetic mucins

Wardzala, Casia L.; Clauss, Zachary S.; Kramer, Jessica R.

doi:10.3389/fcell.2022.952931

Cited by 4 publications

(4 citation statements)

References 64 publications

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“…Toxic effects were unexpected since native AFGPs are present at up to 25 mg/mL in fish blood 1 and similar synthetic glycopolypeptides are nontoxic. 92 Considering their validated internalization behavior, we assessed (βGalαGalNAcT 0.33 -s-A 0.66 ) 57 with HEK293 cells. CCK8 assays were conducted after 24 h at 37 °C with sAFGP concentrations relevant to IRI.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Synthetic Antifreeze Glycoproteins with Potent Ice-Binding Activity

Deleray,

Saini,

Wallberg

et al. 2024

Chem. Mater.

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Antifreeze glycoproteins (AFGPs) are produced by extremophiles to defend against tissue damage in freezing climates. Cumbersome isolation from polar fish has limited probing AFGP molecular mechanisms of action and limited development of bioinspired cryoprotectants for application in agriculture, foods, coatings, and biomedicine. Here, we present a rapid, scalable, and tunable route to synthetic AFGPs (sAFGPs) using N-carboxyanhydride polymerization. Our materials are the first mimics to harness the molecular size, chemical motifs, and long-range conformation of native AFGPs. We found that ice-binding activity increases with chain length, Ala is a key residue, and the native protein sequence is not required. The glycan structure had only minor effects, and all glycans examined displayed antifreeze activity. The sAFGPs are biodegradable, nontoxic, internalized into endocytosing cells, and bystanders in cryopreservation of human red blood cells. Overall, our sAFGPs functioned as surrogates for bona fide AFGPs, solving a long-standing challenge in accessing natural antifreeze materials.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Synthetic Antifreeze Glycoproteins with Potent Ice-Binding Activity

Deleray,

Saini,

Wallberg

et al. 2024

Chem. Mater.

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“…Considering that some proteases prefer to cleave near hydrophobic residues, we rationalized that the presence or absence of A L/D might further tune synMUC proteolytic susceptibility. Additionally, the utility of similar l -stereochemistry glycopolypeptides has been well studied by our lab and others. − …”

Section: Resultsmentioning

confidence: 98%

Mirror Image Mucins and Thio Mucins with Tunable Biodegradation

2023

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Mucin glycoproteins are the major component of mucus and are integral to the cellular glycocalyx. Mucins play diverse roles in health and disease, are an important element in epithelial tissue models, and have broad therapeutic potential. All mucin applications are currently challenged by their inherent structural heterogeneity and degradation by proteases. In this study, we describe the synthesis and study of chemically defined mucin analogues bearing native glycans. We utilized combinations of enantiomer amino acids and glycan thioether linkages to achieve tunable proteolysis while maintaining cytocompatibility and binding activity. Structural characterization revealed a previously unknown mirror-image helix and sheds light on the molecular drivers of glycoprotein conformation. This work represents an important step toward the development of artificial mucins for biomedical applications.

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“…Various similar synthetic glycopolypeptides have been shown by our lab and others to be nontoxic and well tolerated by human cells. 41,83,84 Therefore, we did not expect toxicity or proliferation to be impacted for our sAFGPs. To verify this, we conducted CCK8 assays in human embryonic kidney (HEK) 293 cells.…”

Section: ■ Resultsmentioning

confidence: 99%

Glycosylated Polyhydroxyproline Is a Potent Antifreeze Molecule

McPartlon,

Osborne,

Kramer

2024

Biomacromolecules

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Molecules that inhibit the growth of ice crystals are highly desirable for applications in building materials, foods, and agriculture. Antifreezes are particularly essential in biomedicine for tissue banking, yet molecules currently in use have known toxic effects. Antifreeze glycoproteins have evolved naturally in polar fish species living in subzero climates, but practical issues with collection and purification have limited their commercial use. Here, we present a synthetic strategy using polymerization of amino acid N-carboxyanhydrides to produce polypeptide mimics of these potent natural antifreeze proteins. We investigated a set of mimics with varied structural properties and identified a glycopolypeptide with potent ice recrystallization inhibition properties. We optimized for molecular weight, characterized their conformations, and verified their cytocompatibility in a human cell line. Overall, we present a material that will have broad applications as a biocompatible antifreeze.

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Principles of glycocalyx engineering with hydrophobic-anchored synthetic mucins

Cited by 4 publications

References 64 publications

Synthetic Antifreeze Glycoproteins with Potent Ice-Binding Activity

Synthetic Antifreeze Glycoproteins with Potent Ice-Binding Activity

Mirror Image Mucins and Thio Mucins with Tunable Biodegradation

Glycosylated Polyhydroxyproline Is a Potent Antifreeze Molecule

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