Zlatanic V

References (2)

Title : Cover Picture: Discovery of New Classes of Compounds that Reactivate Acetylcholinesterase Inhibited by Organophosphates (ChemBioChem 15\/2015) - Katz_2015_Chembiochem_16_2113
Author(s) : Katz FS , Pecic S , Tran TH , Trakht I , Schneider L , Zhu Z , Ton-That L , Luzac M , Zlatanic V , Damera S , MacDonald J , Landry DW , Tong L , Stojanovic MN
Ref : Chembiochem , 16 :2113 , 2015
Abstract : The cover picture shows that a mouse exposed to otherwise lethal doses of an organophosphorous agent survives if it is treated with compounds that we recently identified as reactivators of organopsphate-inhibited acetylcholinesterase (AChE). We have demonstrated that survival correlates with reactivation of AChE activity across a panel of tissues, including brain tissues across the blood-brain barrier. We have also determined the co-crystal of one of these reactivators bound to organophosphate-inhibited AChE and found that it binds in a unique manner to the enzyme, forming a dimer within the active site. These compounds were also efficient at reactivating the human form of AChE, thus indicating that their protective effects could be translated for human use. Molecular graphics for the cover were performed with the UCSF Chimera package. Chimera is developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIGMS P41-GM103311).
ESTHER : Katz_2015_Chembiochem_16_2113
PubMedSearch : Katz_2015_Chembiochem_16_2113
PubMedID: 26444304

Title : Discovery of New Classes of Compounds that Reactivate Acetylcholinesterase Inhibited by Organophosphates - Katz_2015_Chembiochem_16_2205
Author(s) : Katz FS , Pecic S , Tran TH , Trakht I , Schneider L , Zhu Z , Ton-That L , Luzac M , Zlatanic V , Damera S , MacDonald J , Landry DW , Tong L , Stojanovic MN
Ref : Chembiochem , 16 :2205 , 2015
Abstract : Acetylcholinesterase (AChE) that has been covalently inhibited by organophosphate compounds (OPCs), such as nerve agents and pesticides, has traditionally been reactivated by using nucleophilic oximes. There is, however, a clearly recognized need for new classes of compounds with the ability to reactivate inhibited AChE with improved in vivo efficacy. Here we describe our discovery of new functional groups-Mannich phenols and general bases-that are capable of reactivating OPC-inhibited AChE more efficiently than standard oximes and we describe the cooperative mechanism by which these functionalities are delivered to the active site. These discoveries, supported by preliminary in vivo results and crystallographic data, significantly broaden the available approaches for reactivation of AChE.
ESTHER : Katz_2015_Chembiochem_16_2205
PubMedSearch : Katz_2015_Chembiochem_16_2205
PubMedID: 26350723
Gene_locus related to this paper: mouse-ACHE