应用化学 ›› 2022, Vol. 39 ›› Issue (10): 1475-1487.DOI: 10.19894/j.issn.1000-0518.220032
• 综合评述 • 下一篇
郭琳洁1,2,3, 彭红珍2, 李江1,2,3, 王丽华1,2,3, 诸颖1,2,3()
收稿日期:
2022-02-11
接受日期:
2022-04-14
出版日期:
2022-10-01
发布日期:
2022-10-05
通讯作者:
诸颖
基金资助:
Lin-Jie GUO1,2,3, Hong-Zhen PENG2, Jiang LI1,2,3, Li-Hua WANG1,2,3, Ying ZHU1,2,3()
Received:
2022-02-11
Accepted:
2022-04-14
Published:
2022-10-01
Online:
2022-10-05
Contact:
Ying ZHU
About author:
zhuying@zjlab.org.cnSupported by:
摘要:
细胞表面受体与配体之间的特异性相互作用在细胞生物学过程中起着重要作用。然而,与均相溶液不同,受体分子在细胞膜上的分布是非连续的、动态的,因此细胞表面的受体配体相互作用通常呈现复杂的非线性结合模式。框架核酸作为一类具有确定几何形状的DNA纳米支架,可用于多价配体的偶联,为深入揭示受体配体相互作用机制提供了可靠的工具。利用框架核酸纳米分辨率的可寻址特性,可实现对配体数目、间距及空间构象等参数的精确调控,进而研究细胞表面受体配体的结合特性及影响因素,优化结合条件最终实现高效的分子识别及靶向治疗。本文综述了基于框架核酸的细胞表面受体配体相互作用研究进展,通过探讨细胞表面受体配体相互作用的重要影响因素及生物学应用,对该研究领域的发展前景和未来趋势予以展望。
中图分类号:
郭琳洁, 彭红珍, 李江, 王丽华, 诸颖. 基于框架核酸的细胞表面受体配体相互作用研究进展[J]. 应用化学, 2022, 39(10): 1475-1487.
Lin-Jie GUO, Hong-Zhen PENG, Jiang LI, Li-Hua WANG, Ying ZHU. Advances in Receptor‑ligand Interactions on Cell Surface Based on Framework Nucleic Acids[J]. Chinese Journal of Applied Chemistry, 2022, 39(10): 1475-1487.
图1 DNA与配体的非共价连接与共价连接(a) 可卡因酯酶CocE通过生物素亲和素非共价相互作用连接在DNA折纸的指定位点[19]; (b) 带His标签的EGFP蛋白在Ni2+离子存在下,与氮三乙酸(NTA)标记的DNA非共价连接[22]; (c) SPDP、SMCC、SNAP-tag和Halo-tag介导的DNA与配体的共价连接作用机制[16]
Fig.1 Non-covalent and covalent conjugation between DNA and ligands(a) The cocaine-esterase CocE non-covalently linked to the specified site of DNA origami through streptavidin and biotin interactions[19]; (b) EGFP protein with Histag non-covalently linked to NTA-DNA in the presence of Ni2+[22]; (c) SPDP, SMCC, Snap-tag and Halo-tag mediated covalent conjugation[16]
图2 基于框架核酸的受体配体多价相互作用(a) 基于自组装DNA“纳米蜈蚣”的多价核酸适配体[20]; (b) 三角形DNA折纸上修饰多价EGF和A20FMDV2多肽用于癌细胞扩散中受体配体相互作用研究[42]; (c) DNA四面体作为支架在微流体芯片界面上形成多价核酸适配体,对循环肿瘤细胞进行捕获与释放[49]
Fig.2 Multivalent interactions between receptor and ligand based on framework nucleic acids(a) Multivalent aptamers conjugated to self-assembled DNA “nanocentipede”[20]; (b) EGF and A20FMDV2 peptides modified on triangular DNA origami for the study of receptor ligand interactions in cancer cell proliferation[42]; (c) DNA tetrahedron with multivalent aptamers on the microfluidic chip interface for circulating tumor cells capture and release[49]
图3 基于框架核酸的受体配体距离依赖的相互作用(a) DNA三角折纸上不同距离人工抗原表位设计及高速原子力显微镜下抗原抗体相互作用的单分子成像[61]; (b) eOD-GT8抗原以不同数目和间距连接在二十面体及六螺旋DNA折纸表面[62]; (c) 方块折纸两个垂直方向上不同距离caspase-9单体的原子力显微镜成像[63]
Fig.3 Distance-dependent interactions between receptor and ligand based on framework nucleic acids(a) Design of artificial antigen epitopes with different distances on DNA triangular origami and single-molecule imaging of antigen-antibody interactions under high-speed atomic force microscopy[61]; (b) eOD-GT8 antigens attached to icosahedral and six-helix DNA origami surfaces in varying numbers and intervals[62]; (c) Atomic force microscopy imaging of caspase-9 monomer at different distances in two vertical directions on square DNA origami[63]
图4 基于框架核酸的受体配体拓扑构象依赖的相互作用(a) 基于DNA四面体的核酸适配体拓扑重排及其与细胞膜上受体结合[67]; (b) 根据登革热病毒表面3价与5价包膜蛋白域Ⅲ(ED3)设计的携带10个ED3核酸适配体的星形DNA结构[69]; (c) 二维DNA折纸的纳米空腔上11种核酸适配体构象变化及其与配体的结合率比较[70]
Fig.4 Topologically conformation dependent interactions between receptor and ligand based on framework nucleic acids(a) Topological rearrangement of aptamers based on DNA tetrahedrons and their binding to cell membrane receptors[67]; (b) Star-shaped DNA structure carrying 10 ED3 aptamers based on surface trivalent and pentavalent envelope protein domain Ⅲ (ED3) of dengue virus[69]; (c) Comparison of conformation changes of 11 aptamers and their binding rates with ligands in nanocavities of two-dimensional DNA origami[70]
图5 基于框架核酸的受体配体相互作用的生物学应用(a) 基于DNA四面体的多价核酸适配体用于循环肿瘤细胞捕获[67]; (b) 测量拓扑工程DNA四面体编码的多价核酸适配体与细胞表面受体结合力[68]; (c) 多价核酸适配体结合的DNA折纸作为抗癌药物阿霉素(Dox)的靶向递送载体[75]; (d) 连接核酸适配体的DNA纳米机器人用于凝血酶的靶向递送和响应性释放[78]
Fig.5 Biological applications of receptor-ligand interactions based on framework nucleic acids(a) Multivalent aptamers based on DNA tetrahedrons for circulating tumor cell capture[67]; (b) Measuring the binding force between multivalent aptamers and cell surface receptors encoded by topological engineering DNA tetrahedrons[68]; (c) Multivalent aptamer-conjugated DNA origami as a targeted delivery vector for the anticancer drug Doxorubicin[75]; (d) Targeted delivery and responsive release of thrombin by DNA nanorobots linked with aptamers[78]
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