Accession Number : ADA513540


Title :   Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design


Descriptive Note : Journal article


Corporate Author : MAYO CLINIC ROCHESTER MN


Personal Author(s) : Pang, Yuan-Ping ; Vummenthala, Anuradha ; Mishra, Rajesh K ; Park, Jewn G ; Wang, Shaohua ; Davis, Jon ; Millard, Charles B ; Schmidt, James J


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a513540.pdf


Report Date : Nov 2009


Pagination or Media Count : 19


Abstract : Botulinum neurotoxin serotype A (BoNTA) causes a life-threatening neuroparalytic disease known as botulism. Current treatment for postexposure of BoNTA uses antibodies that are effective in neutralizing the extracellular toxin to prevent further intoxication but generally cannot rescue already intoxicated neurons. Effective small-molecule inhibitors of BoNTA endopeptidase (BoNTAc) are desirable because such inhibitors potentially can neutralize the intracellular BoNTA and offer complementary treatment for botulism. Previously, we reported a serotype-selective, small-molecule BoNTAc inhibitor with a K1pp value of 3.8 0.8 M. This inhibitor was developed by lead identification using virtual screening followed by computer-aided optimization of a lead with an IC50 value of 100 m.


Descriptors :   *CLOSTRIDIUM BOTULINUM , *COMPUTER AIDED DESIGN , *NEUROTOXINS , COMPUTER APPLICATIONS , NERVE CELLS , INHIBITORS , SEROLOGY , TOXINS AND ANTITOXINS , VIRTUAL REALITY , BACTERIAL TOXINS , MOLECULES , OPTIMIZATION , REPRINTS , ANTIBODIES


Subject Categories : Microbiology
      Pharmacology
      Computer Programming and Software


Distribution Statement : APPROVED FOR PUBLIC RELEASE