Identification of organophosphate modifications by high‐resolution mass spectrometry

• Published in: Bulletin of the Korean Chemical Society Vol. 43; no. 3; pp. 444 - 449
• Main Authors: Lee, Jun Hyung, Jang, Wooyoung Eric, Park, Ji Hwan, Mohammad, Hazara Begum, Lee, Jin‐Young, Jeong, Woo‐Hyeon, Kim, Min‐Sik
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley‐VCH Verlag GmbH & Co. KGaA 01.03.2022; 대한화학회
• Subjects: human plasma; mass spectrometry; nuerotoxicity; organophosphate; protein modification; 화학
• ISSN: 1229-5949; 0253-2964; 1229-5949
• DOI: 10.1002/bkcs.12478

Organophosphate (OP) compounds exhibit neurotoxicity by binding to serine residues of acetylcholinesterase (AChE) in the cholinergic nervous system and subsequently lead to the accumulation of acetylcholine in neuromuscular junctions of synapses. AChE capable of hydrolyzing choline esters is known to be inhibited in patients with nerve agents poisoning. Since OP is known to be transported by covalent bonding to human serum albumin (HSA), OP‐HSA adducts are considered potential diagnostic markers for OP exposures. In this study, HSA modification sites by OP or OP‐like compounds such as V‐type (VX) and Novichok‐type (A234), insecticide (DFP), and serine protease inhibitor (PMSF) were studied using liquid chromatography‐high‐resolution tandem mass spectrometry. As a result, we have discovered a novel OP‐HSA modification site, Y341. We have treated OP to HSA to discover OP‐related modification sites using a high‐resolution mass spectrometry. Further, we found Y341 site as a novel modification on HSA. With the structural visualization using UCSF Chimera, hydrophobicity and electro‐statistic potential, characteristics of the modification site was further studied.