Molecular chaperones are ubiquitously expressed proteins with wide-ranging functions in the folding and cellular translocation of a variety of proteins. Whereas these house-keeping functions are well recognized and have been the subject of intense investigation, it is now becoming clearer that chaperones are also co-opted in pathogenic cells to carry out disease-specific specialized roles. It is now believed that in pathogenic systems, chaperones abet transformation and allow for the blossoming of the disease phenotype.
HER-kinase expression inhibitors: Identification of compounds that promote Her2 degradation has required cumbersome in vitro analyses involving tissue culture with individual drugs followed by detergent lysis of samples, polyacrylamide gel electrophoresis of cellular proteins, and Western blotting to determine Her2 levels, the methodology being decidedly unsuitable for rapid, high-throughput screening of compound libraries.
In vancomycin-resistant enterococci some of the normal cell wall D-Ala-D-Ala termini are substituted by D-Ala-D-Lac. As a result, vancomycin’s efficacy is diminished over 1000-fold, and the bacteria becomes resistant to the effect of this last-resort drug. We hypothesized that cleaving the altered cell wall component with a small molecule will revert the bacteria sensitive to vancomycin.