title: Using positive-ion electrospray ionization mass spectrometry and H/D exchange study phosphoryl group transfer reactions involved in amino acid ester isopropyl phosphoramidates of Brefeldin A.
abstract: As mini-chemical models, amino acid ester isopropyl phosphoramidates of Brefeldin A (compounds 2a-2d) were synthesized and investigated by electrospray ionization tandem mass spectrometry in combination with H/D exchange. To further confirm the fragments's structures, off-line Fourier transform resonance tandem mass spectrometry (FT-ICR-MS/MS) was also performed. The fragmentation rules of compounds 2a-2d have been summarized and the plausible schemes for the fragmentation pathways were proposed. In this study, one dephosphorylated ion and two phosphorylated ions were observed in ESI-MS(2) spectra of [M+Na](+) ions for compounds 2a-2d. The possible mechanisms about phosphorylation and dephosphorylation were proposed and confirmed by H/D exchange. For the "dephosphorylation" rearrangement, a nitrogen atom was migrated from the phosphoryl group to the carbon atom of Brefeldin A's backbone with losing a molecule of C3H7PO3 (122 Da). For the "phosphorylation" rearrangement, an oxygen atom of one phosphoryl group attacked the sideward phosphorus atom to form a nine-member ring intermediate, then two steps of CH covalent bond cleavage with consecutive migration of hydrogen atom to lose a molecule of C16H20O2 (244 Da). The two proposed rearrangement mechanisms about phosphoryl group transfer might be valuable for the structure analysis of other analogs and provide insights into elucidating the dynamic process of the phosphorylation-dephosphorylation of proteins.
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiang-An South Road, Xiamen 361102, PR China.
authors.forename: Mei-Juan
authors.initials: MJ
authors.lastname: Fang
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiang-An South Road, Xiamen 361102, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiang-An South Road, Xiamen 361102, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liao
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiang-An South Road, Xiamen 361102, PR China.
authors.forename: Ying-Kun
authors.initials: YK
authors.lastname: Qiu
authors.affiliation: The Third Institute of Oceanography of the State Oceanic Administration, Xiamen 361005, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Fang
authors.affiliation: College of Chemistry and Chemical Engineering, Department of Chemistry, Xiamen University, Xiamen 361005, PR China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiang-An South Road, Xiamen 361102, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiang-An South Road, Xiamen 361102, PR China; College of Chemistry and Chemical Engineering, Department of Chemistry, Xiamen University, Xiamen 361005, PR China.
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiang-An South Road, Xiamen 361102, PR China. Electronic address: wuzhen@xmu.edu.cn.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000577:Amides / Q000737:chemistry*; D020126:Brefeldin A / Q000737:chemistry*; D041961:Deuterium Exchange Measurement; D010756:Phosphoric Acids / Q000737:chemistry*; D010766:Phosphorylation; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000577:Amides; D010756:Phosphoric Acids; D020126:Brefeldin A; C011067:phosphoramidic acid
keywords: Amino acid ester isopropyl phosphoramidates of Brefeldin A; ESI-FT-ICR-MS; ESI-MS(n); H/D exchange; Phosphoryl group transfer