Bioorthogonal Functionalization of Material Surfaces with Bioactive Molecules.

Bioorthogonal Functionalization of Material Surfaces with Bioactive Molecules.
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具有生物活性分子的材料表面的生物正交功能化。

DOI:
10.1021/acsami.2c20942
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发表时间:
2023
影响因子:
9.5
通讯作者:
Izgu,EnverCagri
Izgu,EnverCagri
中科院分区:
材料科学2区
文献类型:
--
作者:
Hast,Kern;Stone,MRhiaL;Jia,Zhaojun;Baci,Melih;Aggarwal,Tushar;Izgu,EnverCagri

文献摘要

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材料表面的生物活性分子功能化对于生命科学,生物技术和医学技术至关重要。然而,用目前的合成方法实现生物相容性和生物正交性仍然是一个挑战。我们在此报告了一种新的表面官能化方法,该方法在没有游离过渡金属催化剂的情况下进行化学选择性。在该方法中,首先通过酪氨酸酶催化的含四嗪的儿茶酚胺(DOPA-Tet)的推定聚合形成涂层。然后通过四嗪连接将一种或多种类型的含有反式环辛烯的目标分子接枝到涂层上。整个过程在生理条件下进行,适合于接枝具有不同功能和结构复杂性的生物活性分子。利用这种方法,我们用酶(碱性磷酸酶、葡萄糖氧化酶和辣根过氧化物酶)、环肽(环[Arg-Gly-Asp-D-Phe-Lys]或c(RGDfK))和抗生素(万古霉素)功能化材料表面。比色分析证实了表面上的接枝酶的生物催化活性的维护。我们建立了功能化材料与成纤维细胞的哺乳动物细胞相容性。用c(RGDfK)表面功能化显示出改善的成纤维细胞形态和细胞骨架组织。金黄色葡萄球菌的微生物学研究表明,使用DOPA-Tet涂覆的表面抑制生物膜的形成。万古霉素接枝的表面还显示出对血管紧张素的显著抑制。金色生长
The functionalization of material surfaces with biologically active molecules is crucial for enabling technologies in life sciences, biotechnology, and medicine. However, achieving biocompatibility and bioorthogonality with current synthetic methods remains a challenge. We report herein a novel surface functionalization method that proceeds chemoselectively and without a free transition metal catalyst. In this method, a coating is first formed via the tyrosinase-catalyzed putative polymerization of a tetrazine-containing catecholamine (DOPA-Tet). One or more types of molecule of interest containingtrans-cyclooctene are then grafted onto the coating via tetrazine ligation. The entire process proceeds under physiological conditions and is suitable for grafting bioactive molecules with diverse functions and structural complexities. Utilizing this method, we functionalized material surfaces with enzymes (alkaline phosphatase, glucose oxidase, and horseradish peroxidase), a cyclic peptide (cyclo[Arg-Gly-Asp-D-Phe-Lys], or c(RGDfK)), and an antibiotic (vancomycin). Colorimetric assays confirmed the maintenance of the biocatalytic activities of the grafted enzymes on the surface. We established the mammalian cytocompatibility of the functionalized materials with fibroblasts. Surface functionalization with c(RGDfK) showed improved fibroblast cell morphology and cytoskeletal organization. Microbiological studies withStaphylococcus aureusindicated that surfaces coated using DOPA-Tet inhibit the formation of biofilms. Vancomycin-grafted surfaces additionally display significant inhibition of planktonicS. aureusgrowth.