Quantification of binding capacity of natural products to target proteins by sensors integrating SERS labeling and photocrosslinked molecular probes

• Published in: Analytica chimica acta Vol. 1317; p. 342911
• Main Authors: Xie, Jianhui, Mao, Shuying, Zhao, Yanglan, Zhang, Guimin, Yao, Jingchun, Guan, Yongxia, Yan, Jizhong, Zhang, Hui
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.08.2024
• Subjects: Active ingredient; alpha-Glucosidases - chemistry; alpha-Glucosidases - metabolism; Binding capacity; Biological Products - analysis; Biological Products - chemistry; Cross-Linking Reagents - chemistry; Drug discovery; Molecular Probes - chemistry; Natural products; Photochemical Processes; Photocrosslinked molecular probe; Protein Binding; SERS; Silver - chemistry; Spectrum Analysis, Raman - methods; Active ingredient; Binding capacity; Drug discovery; Natural products; SERS; Photocrosslinked molecular probe
• ISSN: 0003-2670; 1873-4324; 1873-4324
• DOI: 10.1016/j.aca.2024.342911

Natural products-based screening of active ingredients and their interactions with target proteins is an important ways to discover new drugs. Assessing the binding capacity of target proteins, particularly when multiple components are involved, presents a significant challenge for sensors. As far as we know, there is currently no sensor that can accomplish high-throughput quantitative analysis of natural product-target protein binding capacity based on Raman spectroscopy. In this study, a novel sensor model has been developed for the quantitative analysis of binding capacity based on Surface-Enhanced Raman Spectroscopy (SERS) and Photocrosslinked Molecular Probe (PCMP) technology. This sensor, named SERS-PCMP, leverages the high throughput of molecular probe technology to investigate the active ingredients in natural products, along with the application of SERS labelling technology for target proteins. Thus it significantly improves the efficiency and accuracy of target protein identification. Based on the novel strategy, quantitative analysis of the binding capacity of 20 components from Shenqi Jiangtang Granules (SJG) to α-Glucosidase were completed. Ultimately, the binding capacity of these active ingredients was ranked based on the detected Raman Intensity. The compounds with higher binding capacity were Astragaloside IV (Intensity, 138.17), Ginsenoside Rh2 (Intensity, 87.46), Ginsenoside Rg3 (Intensity, 73.92) and Ginsenoside Rh1 (Intensity, 64.37), which all exceeded the binding capacity of the positive drug Acarbose (Intensity, 28.75). Furthermore, this strategy also performed a high detection sensitivity. The limit of detection for the enzyme using 0.1 mg of molecular probe magnetic nanoparticles (MP MNPs) was determined to be no less than 0.375 μg/mL. SERS-PCMP sensor integrating SERS labeling and photocrosslinked molecular probes which offers a fresh perspective for future drug discovery studies. Such as high-throughput drug screening and the exploration of small molecule-target protein interactions in vitro. [Display omitted] •A novel SERS-PCMP strategy was designed.•This new strategy was used for exploration of molecule-protein interactions.•Molecule probes were modified on MNPs by photocrosslinking.•New sensor model integrating molecular probes and SERS labelling.•Quantification of natural product bio-activity based on Raman was achieved.