KMS Chongqing Institute of Green and Intelligent Technology, CAS
| Temperature- and pH-dependent protein conformational changes investigated by terahertz dielectric spectroscopy | |
Zang, Ziyi1,2,3; Yan, Shihan2,3 ; Hana, Xiaohui1,3; Wei, Dongshan2,4; Cui, Hong-Liang1,2,3; Du, Chunlei3
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| 2019-05-01 | |
| 摘要 | Polypeptides and protein drugs have received enormous attention from pharmaceutical industry, medical sector and consumer groups because of a favourable combination of their bioactivity, specificity and overall success rate for the treatment of a variety of diseases. The efficacy and safety of drugs may be degraded due to fluctuating environmental factors, accompanied by changes of the natural conformation of protein. Thus, it is necessary and meaningful to evaluate drug status before use. To that end, the evolving new and pre-existing protein activity/conformation technologies have proven to ensure the safety of drug use consistently. Recently, terahertz time-domain spectroscopy (THz-TDS) has demonstrated suitability for label-free and non-destructive detection of polypeptide and protein conformational changes. In this paper, THz optical parameters of pepsin solutions under different temperatures and with varying pH are measured to demonstrate the feasibility and the considerable potential of THz spectroscopic method in detecting protein drugs. In cases where temperature or pH change is apparent, the THz absorption coefficient, the refractive index, and the dielectric loss tangent change noticeably, independently verified by enzyme activity testing. These findings strongly support the conclusion that THz spectroscopy of pepsin solutions can be used for qualitative analysis to identify the folding or unfolding of protein drugs caused by changes of environmental factors, laying the foundation of a new label-free method for quality control of protein drugs. |
| 关键词 | Terahertz dielectric spectroscopy Protein formulation Protein unfolding Temperature pH |
| DOI | 10.1016/j.infrared.2019.03.021 |
| 发表期刊 | INFRARED PHYSICS & TECHNOLOGY
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| ISSN | 1350-4495 |
| 卷号 | 98页码:260-265 |
| 收录类别 | SCI |
| WOS记录号 | WOS:000471361000032 |
| 语种 | 英语 |
