1. COMBINES-CID: An Efficient Method for De Novo Engineering of Highly Specific Chemically Induced Protein Dimerization Systems
- Author
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Huayi Jiang, Frank DiMaio, Shoukai Kang, Molly Jahn, Kristian Davidsen, Liangcai Gu, Mahmoud Moussa, Luis Gomez-Castillo, Zengpeng Li, Yu Liang, and Xiaonan Fu
- Subjects
Ligand ,Chemistry ,Small molecule ligand ,General Chemistry ,Protein engineering ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Small molecule ,Combinatorial chemistry ,Catalysis ,0104 chemical sciences ,Colloid and Surface Chemistry ,Chemically induced dimerization ,Selectivity ,Protein Dimerization ,Biosensor - Abstract
Chemically induced dimerization (CID) systems, in which two proteins dimerize only in the presence of a small molecule ligand, offer versatile tools for small molecule sensing and actuation. However, only a handful of CID systems exist and creating one with the desired sensitivity and specificity for any given ligand is an unsolved problem. Here, we developed a combinatorial binders-enabled selection of CID (COMBINES-CID) method broadly applicable to different ligands. We demonstrated a proof-of-principle by generating nanobody-based heterodimerization systems induced by cannabidiol with high ligand selectivity. We applied the CID system to a sensitive sandwich enzyme-linked immunosorbent assay-like assay of cannabidiol in body fluids with a detection limit of ∼0.25 ng/mL. COMBINES-CID provides an efficient, cost-effective solution for expanding the biosensor toolkit for small molecule detection.
- Published
- 2019
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