title: Characterization of the selective alkylation site in hemoglobin A by dihydroartemisinin with tandem mass spectrometry.
abstract: The reaction between the antimalarial drug dihydroartemisinin (DHA) and hemoglobin A (HbA) was investigated in vitro. A fluorescein-tagged artemisinin analog reacted with HbA and fluorescent HbA-drug adducts could be visualized on SDS-PAGE to confirm stable covalent reaction adducts and necessity of the endoperoxide moiety and Fe(II). Mass spectrometric analyses revealed that DHA favourably alkylated protein part rather than heme and the modification site was identified to be at Tyr35 of the beta globin chain.
authors.affiliation: Department of Chemistry and Center for Excellence in Protein and Enzyme Technology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Khomsan
authors.initials: K
authors.lastname: Tiensomjitr
authors.affiliation: Department of Chemistry and Center for Excellence in Protein and Enzyme Technology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Samran
authors.initials: S
authors.lastname: Prabpai
authors.affiliation: Department of Chemistry and Center for Excellence in Protein and Enzyme Technology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand. Electronic address: palangpon.kon@mahidol.ac.th.
authors.forename: Palangpon
authors.initials: P
authors.lastname: Kongsaeree
mesh_terms: D000478:Alkylation / Q000187:drug effects; D000962:Antimalarials / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D037621:Artemisinins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D005456:Fluorescent Dyes / Q000737:chemistry; D006441:Hemoglobin A / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D053719:Tandem Mass Spectrometry; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D005456:Fluorescent Dyes; D014443:Tyrosine; C039060:artenimol; D006441:Hemoglobin A
keywords: Artemisinin; Hemoglobin; Selective modification