selective and irreversible inhibitors of mosquito acetylcholinesterases for controlling malaria and other mosquito-borne diseases蚊子的选择性和不可逆抑制剂乙酰胆碱酯酶控制疟疾和其他蚊媒疾病.pdfVIP

Selective and Irreversible Inhibitors of Mosquito Acetylcholinesterases for Controlling Malaria and Other Mosquito-Borne Diseases 1 ¨ 2 1 1 3 3 Yuan-Ping Pang *, Fredrik Ekstrom *, Gregory A. Polsinelli , Yang Gao , Sandeep Rana , Duy H. Hua , ¨ 2 2 1 1¤ 1 4 Bjorn Andersson , Per Ola Andersson , Lei Peng , Sanjay K. Singh , Rajesh K. Mishra , Kun Yan Zhu , 5 5 1 Ann M. Fallon , David W. Ragsdale , Stephen Brimijoin * 1 Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, United States of America, 2 Swedish Defence Research Agency, CBRN ˚ Defence and Security, Umea, Sweden, 3 Department of Chemistry, Kansas State University, Manhattan, Kansas, United States of America, 4 Department of Entomology, Kansas State University, Manhattan, Kansas, United States of America, 5 Department of Entomology, University of Minnesota, Saint Paul, Minnesota, United States of America Abstract New insecticides are urgently needed because resistance to current insecticides allows resurgence of disease-transmitting mosquitoes while concerns for human toxicity from current compounds are growing. We previously reported the finding of a free cysteine (Cys) residue at the entrance of the active site of acetylcholinesterase (AChE) in some insects but not in mammals, birds, and fish. These insects have two AChE genes (AP and AO), and only AP-AChE carries the Cys residue. Most of these insects are disease v