Method for the treatment of microorganism infections by inhibiting energy storage and utilization

Abstract

A method and pharmaceutical composition for inhibiting infections of pathogenic microorganisms by inhibiting the production of ADP-glucose, particularly by inhibiting the activity of ADP-glucose pyrophosphorylase or glycogen synthase.

1 - 31 . (canceled)  
     
     
         32 . A method of identifying a compound that inhibits glycogen synthesis in pathogenic bacteria, comprising: 
 a. exposing a test compound to an enzyme that is part of a glycogen biosynthesis pathway in a pathogenic bacteria, wherein the enzyme exhibits a catalytic activity not found in mammals, and wherein the exposure occurs under conditions that, in the absence of an inhibitor, allow the enzyme to exhibit the catalytic activity; and    b. determining if the test compound inhibits the catalytic activity of the enzyme, and, if so, identifying the test compound as an inhibitor of glycogen synthesis in pathogenic bacteria.    
     
     
         33 . A method according to  claim 32  wherein the pathogenic bacteria is selected from the group consisting of  Chlamydia pneumoniae, Chlamydia trachomatis, Esherichia coli  O157,  Haemophilus influenzae, Mycobacterium leprae, Mycobacterium tuberculosis, Salmonella typhimurium  and  Vibrio cholerae, Streptococcus pneumoniae, Yersinia pestis, Bacillus subtilus, and    Bacillus anthracis.    
     
     
         34 . A method according to  claim 32  wherein the enzyme is selected from the group consisting of ADP-glucose pyrophosphorylase and glycogen synthase.  
     
     
         35 . A method according to  claim 32  wherein the enzyme is ADP-glucose pyrophosphorylase.  
     
     
         36 . A method according to  claim 35  wherein the catalytic activity is EC. 2.7.7.27.  
     
     
         37 . A method according to  claim 32  wherein the enzyme is glycogen synthase.  
     
     
         38 . A method according to  claim 37  wherein the catalytic activity is EC. 2.4.1.21.  
     
     
         39 . A method according to  claim 32  that is performed in vitro.  
     
     
         40 . A method according to  claim 32  that is performed while culturing the pathogenic bacteria under growth conditions.  
     
     
         41 . A method according to  claim 32  further comprising determining whether the inhibitor of glycogen synthesis can be used to treat an infection in a mammal caused by the pathogenic bacteria, whereby the inhibitor is administered to a non-human animal having an infection caused by the pathogenic bacteria and progress of the infection is monitored.  
     
     
         42 . An inhibitor of glycogen synthesis in pathogenic bacteria, or a pharmaceutically acceptable salt thereof, wherein the inhibitor is identified by a method according to claim  1  and the inhibitor inhibits an enzyme having a catalytic activity not found in mammals.  
     
     
         43 . An inhibitor according to  claim 42 , wherein the inhibitor inhibits the catalytic activity of an enzyme selected from the group consisting of ADP-glucose pyrophosphorylase and glycogen synthase.  
     
     
         44 . An inhibitor according to  claim 43  that is an ADP-glucose borano analog.  
     
     
         45 . An inhibitor according to  claim 44  wherein the ADP-glucose borano analog is adenosine α-P-boranodiphosphoglucose.  
     
     
         46 . A method of inhibiting of inhibiting glycogen synthesis in pathogenic bacteria, comprising exposing a pathogenic bacteria to an inhibitor according to  claim 42 .  
     
     
         47 . A method according to  claim 46  wherein the inhibitor inhibits the catalytic activity of an enzyme selected from the group consisting of ADP-glucose pyrophosphorylase and glycogen synthase.  
     
     
         48 . A method according to  claim 47  wherein the inhibitor is an ADP-glucose borano analog or a pharmaceutically acceptable salt thereof.  
     
     
         49 . A method according to  claim 46  wherein the pathogenic bacteria is a source of an infection in a mammal.  
     
     
         50 . A method according to  claim 46  wherein inhibition of glycogen synthesis in the pathogenic bacteria effects treatment of the infection.  
     
     
         51 . A method according to  claim 50  wherein the mammal is a human.