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用于黏膜修复和抗炎药物递送的自组装糖缀合物纳米纤维的设计与合成

Design and Synthesis of Nanofibers of Self-assembled Glycoconjugates towards Mucosal Lining Restoration and Anti-Inflammatory Drug Delivery.

作者信息

Zhou Jie, O'Keeffe Michael, Liao Gongxian, Zhao Fan, Terhorst Cox, Xu Bing

机构信息

Department of Chemistry, Brandeis University, 415 South Street, Waltham, Massachusetts 02454, United States.

Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States.

出版信息

Tetrahedron. 2016 Oct 6;72(40):6078-6083. doi: 10.1016/j.tet.2016.07.057. Epub 2016 Jul 26.

Abstract

The medical practice for IBD is solely based on anti-inflammatory drugs, but the outcome is far from ideal. Our long-term research goal is to seek a better clinical outcome by combining the anti-inflammatory therapy with physical mucus layer restoration. As the first step towards that objective, we choose to develop self-assembled hydrogels of glycoconjugates that consist of anti-inflammatory drugs and glycopeptides. By covalently linking peptides (e.g., nap-phe-phe-lys), saccharides (e.g., glucosamine), and an anti-inflammatory drug (i.e., olsalazine), we have demonstrated that the obtained molecules self-assemble in water to form hydrogels composed of 3D networks of the nanofibers under acidic conditions. We also confirmed that the resulting glycoconjugates are cell compatible. However, the preliminary assessment of the efficacy of the hydrogels on the murine model is inconclusive, which warrants further investigation and molecular engineering.

摘要

炎症性肠病的医学治疗仅基于抗炎药物,但治疗效果远不理想。我们的长期研究目标是通过将抗炎治疗与物理黏液层修复相结合来寻求更好的临床效果。作为实现该目标的第一步,我们选择开发由抗炎药物和糖肽组成的糖缀合物自组装水凝胶。通过将肽(例如,萘-苯丙氨酸-苯丙氨酸-赖氨酸)、糖类(例如,氨基葡萄糖)和一种抗炎药物(即柳氮磺胺吡啶)共价连接,我们已经证明所获得的分子在水中自组装,在酸性条件下形成由纳米纤维三维网络组成的水凝胶。我们还证实所得的糖缀合物具有细胞相容性。然而,水凝胶对小鼠模型疗效的初步评估尚无定论,这需要进一步研究和分子工程设计。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/938a/5312973/d3bfb1884f20/nihms808920f1.jpg

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本文引用的文献

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Carbohydrates in Supramolecular Chemistry.超分子化学中的碳水化合物。
Chem Rev. 2016 Feb 24;116(4):1693-752. doi: 10.1021/acs.chemrev.5b00516. Epub 2015 Dec 24.
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The first CD73-instructed supramolecular hydrogel.首个由CD73指导形成的超分子水凝胶。
J Colloid Interface Sci. 2015 Jun 1;447:269-72. doi: 10.1016/j.jcis.2014.11.050. Epub 2014 Nov 25.

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