bc9b00601_si_001.pdf (3.8 MB)
Glycoprotein Mimics with Tunable Functionalization through Global Amino Acid Substitution and Copper Click Chemistry
journal contribution
posted on 2020-02-20, 15:41 authored by Brian
M. Seifried, Wenjing Qi, Yun Jung Yang, Danielle J. Mai, Wendy B. Puryear, Jonathan A. Runstadler, Guosong Chen, Bradley D. OlsenGlycoproteins and their mimics are
challenging to produce because
of their large number of polysaccharide side chains that form a densely
grafted protein–polysaccharide brush architecture. Herein a
new approach to protein bioconjugate synthesis is demonstrated that
can approach the functionalization densities of natural glycoproteins
through oligosaccharide grafting. Global amino acid substitution is
used to replace the methionine residues in a methionine-enriched elastin-like
polypeptide with homopropargylglycine (HPG); the substitution was
found to replace 93% of the 41 methionines in the protein sequence
as well as broaden and increase the thermoresponsive transition. A
series of saccharides were conjugated to the recombinant protein backbones
through copper(I)-catalyzed alkyne–azide cycloaddition to determine
reactivity trends, with 83–100% glycosylation of HPGs. Only
an acetyl-protected sialyllactose moiety showed a lower level of 42%
HPG glycosylation that is attributed to steric hindrance. The recombinant
glycoproteins reproduced the key biofunctional properties of their
natural counterparts such as viral inhibition and lectin binding.
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Tunable Functionalizationthermoresponsive transitionprotein bioconjugate synthesisGlycoprotein Mimicsglycoproteinacetyl-protected sialyllactose moietyfunctionalization densitiesmethionine-enriched elastin-like polypeptidelectin binding41 methioninesprotein sequencebiofunctional propertiesCopper Click Chemistry Glycoproteinssteric hindranceGlobal Aminoprotein backbonespolysaccharide side chainsacid substitutionHPGreactivity trendsglycosylationmethionine residues
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