Taichi Misako, Nomura Shogo, Nakase Ikuhiko, Imamaki Rie, Kizuka Yasuhiko, Ota Fumi, Dohmae Naoshi, Kitazume Shinobu, Taniguchi Naoyuki, Tanaka Katsunori
Biofunctional Synthetic Chemistry Laboratory RIKEN Hirosawa Wako-shi Saitama 351-0198 Japan.
Nanoscience and Nanotechnology Research Center Research Organization of the 21st Century Osaka Prefecture University 1-2 Gakuen-cho, Naka Sakai Osaka 599-8570 Japan.
Adv Sci (Weinh). 2017 Jul 28;4(11):1700147. doi: 10.1002/advs.201700147. eCollection 2017 Nov.
This paper reports an entirely unexplored concept of simultaneously recognizing two receptors using high- and low-affinity ligands through ligating them in situ on the target cell surface. This de novo approach is inspired by the pretargeting strategy frequently applied in molecular imaging, and has now evolved as the basis of a new paradigm for visualizing target cells with a high imaging contrast. A distinct advantage of using a labeled low-affinity ligand such as glycan is that the excess labeled ligand can be washed away from the cells, whereas the ligand bound to the cell, even at the milli molar affinity level, can be anchored by a bioorthogonal reaction with a pretargeted high-affinity ligand on the surface. Consequently, nonspecific background is minimized, leading to improved imaging contrast. Importantly, despite previously unexplored for molecular imaging, a notoriously weak glycan/lectin interaction can now be utilized as a highly selective ligand to the targets.
本文报道了一种全新的概念，即通过在靶细胞表面原位连接高亲和力和低亲和力配体来同时识别两种受体。这种从头开始的方法受到分子成像中经常应用的预靶向策略的启发，现已发展成为一种用于以高成像对比度可视化靶细胞的新范式的基础。使用诸如聚糖之类的标记低亲和力配体的一个显著优点是，过量的标记配体可以从细胞中洗去，而与细胞结合的配体，即使处于毫摩尔亲和力水平，也可以通过与表面上预靶向的高亲和力配体进行生物正交反应而锚定。因此，非特异性背景被最小化，从而提高了成像对比度。重要的是，尽管此前在分子成像中未被探索过，但一种 notoriously（此处疑为notoriously拼写错误，意为“众所周知地”）弱的聚糖/凝集素相互作用现在可以用作对靶标的高度选择性配体。
