2025-06-03 京都大学
生きている動物の脳内の特定受容体上で蛍光センサー分子を構築
<関連情報>
- https://www.t.kyoto-u.ac.jp/ja/research/topics/20250602
- https://www.t.kyoto-u.ac.jp/ja/research/topics/r70602seika_nonaka
- https://www.nature.com/articles/s44160-025-00815-6
リガンド指向性化学とクリック化学による受容体を基体としたプロテアーゼセンサーの脳内合成 In-brain synthesis of receptor-based protease sensors by coupling ligand-directed chemistry and click chemistry
Seiji Sakamoto,Kazuki Shiraiwa,Mengchu Wang,Mamoru Ishikawa,Hiroshi Nonaka & Itaru Hamachi
Nature Synthesis Published:02 June 2025
DOI:https://doi.org/10.1038/s44160-025-00815-6
Abstract
The chemical modification of natural proteins in living systems is highly desirable as cutting-edge research at the chemistry–biology interface. Recent advances in bio-orthogonal protein modification have enabled the production of chemically functionalized proteins in cultured cell systems. However, a limited number of methods are applicable in vivo because of the complexity of the three-dimensional constructs of living systems with diverse, heterogeneous cell populations and flow systems filled with tissue fluids. Here we report a genetic-engineering-free method to modify receptor proteins with various probes in the living mouse brain by combining in-brain ligand-directed chemistry with bio-orthogonal click chemistry, and propose a chemical guideline for the reaction design. The rapid and selective tethering of a set of fluorescent peptides to AMPA-type glutamate receptors allowed the synthesis of receptor-based fluorescent sensors. These probes enabled mapping of the activity of matrix metalloproteinase-9 proximal to AMPA-type glutamate receptors in the living brain to be realized with high spatial resolution.
