Structure-Directed Screening and Analysis of Thyroid-Disrupting Chemicals Targeting Transthyretin Based on Molecular Recognition and Chromatographic Separation

• Published in: Environmental science & technology 2020-05, Vol.54 (9), p.5437-5445
• Main Authors: Huang, Kai, Wang, Xiu, Zhang, Hongxing, Zeng, Lingshuai, Zhang, Xiu, Wang, Bingmao, Zhou, Yikai, Jing, Tao
• Format: Article
• Language: English
• Subjects: Amino acids; Binders; Binding; Chemicals; Chromatography; Composite materials; Disruption; Health risks; Molecular imprinting; Retention; Screening; Separation; Thyroid; Thyroid gland; Thyroxine; Transthyretin; Tryptophan
• ISSN: 0013-936X; 1520-5851
• DOI: 10.1021/acs.est.9b05761

Exposure to thyroid-disrupting chemicals (TDCs) poses a great threat to human health. However, the screening and analysis of TDCs in environmental samples remain a tough work. In this study, we reported a structure-directed strategy for analyzing TDCs targeting transthyretin (TTR) based on molecular imprinting and chromatographic separation. The imprinted composites were prepared using l-thyroxine (T4) as a template and a tryptophan-like monomer screened from the amino acid library. The imprinted composites exhibited an adsorption capacity of 22.2 μmol g–1 for T4 and an imprinting factor of 2.1. Chromatographic testing was then conducted among 72 chemicals using the imprinted composites-packed column. High retention factors were observed for chemicals that were structurally similar to T4. The chromatographic results were compared with a data set of 45 chemicals with known activities toward TTR. The results suggested that chemicals can be distinguished as TTR binders and nonbinders by retention factors, with a predictive accuracy of more than 90%. Moreover, the retention factors of chemicals were highly correlated with the reported relative potencies obtained from TTR assays. Thus, screening of TTR-binding chemicals can be realized through this simple chromatographic method. The imprinted composites were applied for target analysis and nontarget analysis of TTR-binding chemicals in dust samples. Three new TTR binders were successfully identified and verified by this method. The combination of molecular imprinting and chromatography opens up a new approach for screening TDCs targeting TTR.