Department of Chemistry and Chemical Biology, Rutgers University, New Brunswick, New Jersey 08854, United States.
Cancer Pharmacology Program, Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey 08901, United States.
ACS Appl Mater Interfaces. 2023 Feb 1;15(4):4996-5009. doi: 10.1021/acsami.2c20942. Epub 2023 Jan 17.
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 containing -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 with indicated that surfaces coated using DOPA-Tet inhibit the formation of biofilms. Vancomycin-grafted surfaces additionally display significant inhibition of planktonic growth.
将具有生物活性的分子功能化到材料表面对于实现生命科学、生物技术和医学领域的技术至关重要。然而，用当前的合成方法实现生物兼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功能化方法，该方法具有化学选择性，且无需游离过渡金属催化剂。在该方法中，首先通过漆酶催化的含四嗪儿茶酚胺（DOPA-Tet）的假定聚合形成涂层。然后，通过四嗪键合将含有 -环辛烯的一种或多种感兴趣的分子接枝到涂层上。整个过程在生理条件下进行，适用于接枝具有各种功能和结构复杂性的生物活性分子。利用该方法，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（cyclo[Arg-Gly-Asp-D-Phe-Lys]或 c（RGDfK））和抗生素（万古霉素）对材料表面进行了功能化。比色法测定证实了接枝酶在表面上保持了生物催化活性。我们用成纤维细胞证实了功能化材料的哺乳动物细胞相容性。用 c（RGDfK）进行表面功能化可改善成纤维细胞的形态和细胞骨架组织。用 进行的微生物研究表明，用 DOPA-Tet 涂层的表面可抑制生物膜的形成。接枝万古霉素的表面还可显著抑制浮游 生长。
