Mirror Image Mucins and Thio Mucins with Tunable Biodegradation.
Mirror Image Mucins and Thio Mucins with Tunable Biodegradation.
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DOI：
10.1021/jacs.3c03659
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发表时间：
2023-07
影响因子：
15
通讯作者：
V. Kohout;Casia L. Wardzala;Jessica R. Kramer
中科院分区：
文献类型：
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作者：
V. Kohout;Casia L. Wardzala;Jessica R. Kramer
粘蛋白糖蛋白是粘液的主要成分，是细胞糖萼的组成部分。粘蛋白在健康和疾病中发挥着不同的作用，是上皮组织模型中的重要元素，并且具有广泛的治疗潜力。目前，所有粘蛋白应用都受到其固有结构异质性和蛋白酶降解的挑战。在这项研究中，我们描述了化学定义的粘蛋白类似物轴承天然聚糖的合成和研究。我们利用对映体氨基酸和聚糖硫醚键的组合来实现可调的蛋白水解，同时保持细胞相容性和结合活性。结构表征揭示了一个以前未知的镜像螺旋，揭示了糖蛋白构象的分子驱动因素。这项工作代表了生物医学应用的人工粘蛋白的发展的重要一步。
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.