Biomolecular surfaces that release ligands under electrochemical control
Biomolecular surfaces that release ligands under electrochemical control
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DOI：
10.1021/ja000419p
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发表时间：
2000-05-03
影响因子：
15
通讯作者：
Mrksich, M
中科院分区：
文献类型：
--
作者：
Hodneland, CD;Mrksich, M
任何将接触生物环境的材料的设计都要求材料的表面被定制为与接触生物流体的分子、蛋白质或细胞具有所需的相互作用。需要精确控制这些相互作用的应用得益于在金上使用烷硫酸酯自组装单层（sam），因为这些结构有序的薄膜在用配体和其他部分修饰表面方面提供了前所未有的灵活性。这些特性对于开发在生物流体中具有惰性的单分子膜非常重要，因为它们可以防止蛋白质吸附和细胞粘附，从而为粘附细胞的位置和形状提供了方法。配体附着在这些惰性SAMs上，提供了蛋白质和其他受体选择性结合的表面。例如，呈递肽配体的单层膜已被用于控制细胞的粘附，呈递寡核苷酸的单层膜已被用于探测细胞中的基因表达。生物界面科学的一个新挑战是设计动态底物，可以实时改变配体的显示，从而改变蛋白质和细胞与底物的相互作用。我们之前展示了一种动态SAM，它可以从最初的惰性状态切换到允许Diels-Alder介导的配体固定化的状态，这反过来提供了一种激活蛋白质与底物选择性结合的策略。在这里，我们描述了一类新的动态电活性单层，可以选择性地释放固定化配体。图1所示的单层被设计为在对下层金施加还原电位时释放配体生物素。这种动态特性来源于将生物素连接到单分子层上的醌丙酸酯。以前，醌丙烯酯和酰胺分别被用作醇和胺的保护基团，因为醌的轻微化学还原产生对苯二酚，对苯二酚随着醇或胺的释放而迅速内酯化。位于苯基位置的两个甲基与环上的近端甲基一起统称为“三甲基锁”，用于增加内酯化反应的速率，从而增加配体的释放。为了我们的目的，在配体释放前后，单分子层对蛋白质的非特异性吸附保持惰性是至关重要的。因此，这里使用的单层呈现低密度的电活性系绳（约占总烷硫酸盐的1%），由三（乙二醇）基团包围，因为
The design of any material that will contact a biological environment requires that the surface of the material be tailored to have desired interactions with molecules, proteins, or cells of the contacting biological fluid. Applications that require precise control over these interactions have benefited from the use of self-assembled monolayers (SAMs) of alkanethiolates on gold because these structurally ordered films offer unprecedented flexibility in modifying surfaces with ligands and other moieties. These characteristics were important in developing monolayers that are inert in biological fluidssin that they prevent protein adsorption and cell adhesionswhich provided methods for patterning the positions and shapes of attached cells. 1 The attachment of ligands to these inert SAMs gives surfaces to which proteins and other receptors selectively bind. Monolayers presenting peptide ligands, for example, have been used to control the adhesion of cells, 2 and monolayers presenting oligonucleotides have been used for probing gene expression in cells. 3 A new challenge in biointerfacial science is to design dynamic substrates that can alter, in real-time, the display of ligands and, hence, the interactions of proteins and cells with the substrate. 4 We previously demonstrated a dynamic SAM that could be switched from a state that is initially inert to a state that permits the Diels-Alder mediated immobilization of ligands, which in turn provides a strategy to activate the selective binding of proteins to a substrate. 5 Here, we describe a new class of dynamic electroactive monolayer that can selectively release immobilized ligands.The monolayer shown in Figure 1 was designed to release the ligand biotin when a reductive potential is applied to the underlying gold. This dynamic property derives from the quinone propionic ester that tethers the biotin to the monolayer. Previously, quinone propionic esters and amides have been used as protecting groups for alcohols and amines, respectively, because mild chemical reduction of the quinone affords the hydroquinone, which rapidly lactonizes with liberation of an alcohol or amine. 6 The two methyl groups at the benzylic position together with the proximal methyl group on the ringscollectively referred to as the “tri-methyl lock” sserve to increase the rate of the lactonization reaction, and therefore, the release of ligand. 7 For our purposes it is essential that the monolayers remain inert to the nonspecific adsorption of proteinsboth before and after release of the ligand. Accordingly, the monolayers used here present the electroactive tether at low density (approximately 1% of total alkanethiolate) surrounded by tri (ethylene glycol) groups because