Washington University

Gabriel Waksman

Scott J Hultgren

Andrey S Shaw

Frederic G Sauer

Stefan D Knight

Klaus Fuetterer

Michelle Barnhart

Devapriya Choudhury

Many Gram-negative pathogens assemble adhesive pili structures on their surfaces that allow them to colonize host tissues and cause disease. The present invention relates to novel compounds that mimic a chaperone G1 beta-strand or an amino terminal motif of a pilus subunit. The present invention also relates to the complex formed from the binding of such mimic compounds to the hydrophobic groove of a pilus subunit. Competitively interacting with the binding site of pili subunits will negatively affect the chaperone/usher pathway, which is one molecular mechanism by which Gram-negative bacteria assemble adhesive pili structures, and thus prevent or inhibit pilus assembly.

Anti-bacterial compounds directed against pilus biogenesis, adhesion and activity; co-crystals of pilus subunits and methods of use thereof

Modified SH2 domains of intracellular proteins and methods of use, wherein the SH2 domains are modified to include an altered binding site for a signal transduction protein. The binding site is altered to either change the specificity of the SH2 domain for a signal transduction protein that is not the natural ligand or to include a reactive group, such as a reactive amino acid, that reacts with a phosphorylated amino acid of the signal transduction protein. The modified SH2 domains are useful as research tools or in methods for inactivating or inhibiting signal transduction proteins, especially those that contribute to disease or disorders such as cancer or for targeting specific SH2 domains for diagnostics.

Modified SH2 domains

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St. Louis, MO, United States of America

Gabriel Waksman