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Alkylation of human hemoglobin A 0 by the antimalarial drug artemisinin
Author(s) -
Selmeczi Katalin,
Robert Anne,
Claparols Catherine,
Meunier Bernard
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01448-0
Subject(s) - artemisinin , heme , hemoglobin , chemistry , moiety , biochemistry , cofactor , adduct , alkylation , drug , combinatorial chemistry , stereochemistry , plasmodium falciparum , pharmacology , organic chemistry , enzyme , malaria , biology , catalysis , immunology
In vitro, the heme cofactor of human iron(II) hemoglobin was efficiently and quickly alkylated at meso positions by the peroxide‐based antimalarial drug artemisinin, leading to heme–artemisinin‐derived covalent adducts. This reaction occurred in the absence of any added protease or in the presence of an excess of an extra non‐heme protein, or even when artemisinin was added to hemolysed human blood. This activation of artemisinin by the heme moiety of non‐digested hemoglobin clearly indicates the high affinity of this drug for heme, and its efficient alkylating ability under very mild conditions.