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Glycoprotein Mimics with Tunable Functionalization through Global Amino Acid Substitution and Copper Click Chemistry.
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2020-02-20 , DOI: 10.1021/acs.bioconjchem.9b00601 Brian M Seifried 1 , Wenjing Qi 2 , Yun Jung Yang 1 , Danielle J Mai 1 , Wendy B Puryear 3 , Jonathan A Runstadler 3 , Guosong Chen 2 , Bradley D Olsen 1, 4
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2020-02-20 , DOI: 10.1021/acs.bioconjchem.9b00601 Brian M Seifried 1 , Wenjing Qi 2 , Yun Jung Yang 1 , Danielle J Mai 1 , Wendy B Puryear 3 , Jonathan A Runstadler 3 , Guosong Chen 2 , Bradley D Olsen 1, 4
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Glycoproteins 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.
中文翻译：
通过全局氨基酸取代和铜点击化学可调节功能的糖蛋白模拟物。
糖蛋白及其模拟物的生产具有挑战性，因为它们的大量多糖侧链形成了密集嫁接的蛋白-多糖刷结构。本文证明了一种新的蛋白质生物共轭物合成方法，该方法可以通过寡糖接枝接近天然糖蛋白的功能化密度。全局氨基酸取代用于用高炔丙基甘氨酸（HPG）代替富含蛋氨酸的弹性蛋白样多肽中的蛋氨酸残基；发现该取代取代了蛋白质序列中41个蛋氨酸中的93％，并加宽并增加了热响应转变。通过铜（I）催化的炔-叠氮化物环加成反应将一系列糖与重组蛋白主链偶联，以确定反应性趋势，HPG的糖基化率为83-100％。仅乙酰基保护的唾液乳糖部分显示出较低水平的42％HPG糖基化，这归因于位阻。重组糖蛋白复制了其天然对应物的关键生物功能特性，例如病毒抑制和凝集素结合。
更新日期：2020-02-21
中文翻译：
通过全局氨基酸取代和铜点击化学可调节功能的糖蛋白模拟物。
糖蛋白及其模拟物的生产具有挑战性，因为它们的大量多糖侧链形成了密集嫁接的蛋白-多糖刷结构。本文证明了一种新的蛋白质生物共轭物合成方法，该方法可以通过寡糖接枝接近天然糖蛋白的功能化密度。全局氨基酸取代用于用高炔丙基甘氨酸（HPG）代替富含蛋氨酸的弹性蛋白样多肽中的蛋氨酸残基；发现该取代取代了蛋白质序列中41个蛋氨酸中的93％，并加宽并增加了热响应转变。通过铜（I）催化的炔-叠氮化物环加成反应将一系列糖与重组蛋白主链偶联，以确定反应性趋势，HPG的糖基化率为83-100％。仅乙酰基保护的唾液乳糖部分显示出较低水平的42％HPG糖基化，这归因于位阻。重组糖蛋白复制了其天然对应物的关键生物功能特性，例如病毒抑制和凝集素结合。
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