Small-Molecule Patterning via Prefunctionalized Alkanethiols
Small-Molecule Patterning via Prefunctionalized Alkanethiols
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DOI：
10.1021/acs.chemmater.8b00377
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发表时间：
2018-06-26
影响因子：
8.6
通讯作者：
Andrews, Anne M.
中科院分区：
文献类型：
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作者：
Cao, Huan H.;Nakatsuka, Nako;Andrews, Anne M.
小分子和生物分子之间的相互作用在生理学上以及对于生物传感、诊断和治疗应用是重要的。为了研究这些相互作用，可以通过标准偶联化学将小分子拴系到基底上。虽然方便，但这些方法选择了生物识别所需的少数小分子官能团中的一个或多个。此外，对于多路复用，各个探针需要不同的表面官能化化学、条件和/或保护/脱保护策略。因此，当在表面上放置多个小分子时，需要正交化学，其保留所有官能团并且顺序相容。或者，我们通过在合成期间和在Au基底上自组装之前将小分子神经递质前体（例如）偶联到单分散不对称低聚（乙二醇）烷硫醇来实现高保真小分子图案化。我们使用化学剥离光刻技术对衬底进行单次和双次图案化。预官能化硫醇的选择性抗体识别与表面组装后官能化为烷硫醇的小分子的识别相当或更好。这些发现表明，规避连续表面缀合化学的合成和图案化方法能够实现生物分子识别，并为多路复用小分子功能化基底提供门户。
Interactions between small molecules and biomolecules are important physiologically and for biosensing, diagnostic, and therapeutic applications. To investigate these interactions, small molecules can be tethered to substrates through standard coupling chemistries. While convenient, these approaches co-opt one or more of the few small-molecule functional groups needed for biorecognition. Moreover, for multiplexing, individual probes require different surface functionalization chemistries, conditions, and/or protection/deprotection strategies. Thus, when placing multiple small molecules on surfaces, orthogonal chemistries are needed that preserve all functional groups and are sequentially compatible. Alternately, we approach high-fidelity small- molecule patterning by coupling small-molecule neurotransmitter precursors, as examples, to monodisperse asymmetric oligo(ethylene glycol)alkanethiols during synthesis and prior to self-assembly on Au substrates. We use chemical lift-off lithography to singly and doubly pattern substrates. Selective antibody recognition of prefunctionalized thiols was comparable to or better than recognition of small molecules functionalized to alkanethiols after surface assembly. These findings demonstrate that synthesis and patterning approaches that circumvent sequential surface conjugation chemistries enable biomolecule recognition and afford gateways to multiplexed small-molecule functionalized substrates.