Ham Hyun Ok, Park Sung Hyun, Kurutz Josh W, Szleifer Igal G, Messersmith Phillip B
Biomedical Engineering Department, Northwestern University, Evanston, Illinois 60208, United States.
J Am Chem Soc. 2013 Sep 4;135(35):13015-22. doi: 10.1021/ja404681x. Epub 2013 Aug 21.
The glycocalyx of the cell is composed of highly hydrated saccharidic groups conjugated to protein and lipid cores. Although components of the glycocalyx are important in cell-cell interactions and other specific biological recognition events, a fundamental role of the glycocalyx is the inhibition of nonspecific interactions at the cell surface. Inspired by glycoproteins present in the glycocalyx, we describe a new class of synthetic antifouling polymer composed of saccharide containing N-substituted polypeptide (glycopeptoid). Grafting of glycopeptoids to a solid surface resulted in a biomimetic shielding layer that dramatically reduced nonspecific protein, fibroblast, and bacterial cell attachment. All-atom molecular dynamics simulation of grafted glycopeptoids revealed an aqueous interface enriched in highly hydrated saccharide residues. In comparison to saccharide-free peptoids, the interfacial saccharide residues of glycopeptoids formed a higher number of hydrogen bonds with water molecules. Moreover, these hydrogen bonds displayed a longer persistence time, which we believe contributed to fouling resistance by impeding interactions with biomolecules. Our findings suggest that the fouling resistance of glycopeptoids can be explained by the presence of both a 'water barrier' effect associated with the hydrated saccharide residues as well as steric hindrance from the polymer backbone.
细胞的糖萼由与蛋白质和脂质核心结合的高度水合的糖基组成。尽管糖萼的成分在细胞间相互作用和其他特定生物识别事件中很重要，但糖萼的一个基本作用是抑制细胞表面的非特异性相互作用。受糖萼中存在的糖蛋白启发，我们描述了一类由含糖类的N-取代多肽（类糖肽）组成的新型合成防污聚合物。将类糖肽接枝到固体表面会形成一个仿生屏蔽层，该屏蔽层可显著减少非特异性蛋白质、成纤维细胞和细菌细胞的附着。接枝类糖肽的全原子分子动力学模拟显示，富含高度水合糖残基的水相界面。与不含糖类的类肽相比，类糖肽的界面糖残基与水分子形成了更多的氢键。此外，这些氢键的持续时间更长，我们认为这通过阻碍与生物分子的相互作用而有助于抗污。我们的研究结果表明，类糖肽的抗污性可以通过与水合糖残基相关的“水屏障”效应以及聚合物主链的空间位阻来解释。
