Mcmaster University

The Hospital for Sick Children

Eric Brown

Don J Mahuran

Michael B Tropak

Justin D Buttner

Jan E Blanchard

Craig MacNair

Maya Farha

Jonathan Stokes

Jakob Magolan

Xiong Zhang

Nick Jentsch

Lindsey Carfrae

Omar M Elhalfawy

Provided herein are novel synthetic compounds having the structure of formula (1), wherein X is a substituted or unsubstituted aromatic or heteroaromatic mono- or polycyclic ring system; and Y is substituted or unsubstituted C-Calkyl or alkenyl group, or a pharmaceutically acceptable salt thereof. Also provided are pharmaceutical compositions. The compounds and pharmaceutical compositions are useful for inhibiting growth of a bacterium.

Synthetic antibacterial compounds and uses thereof

Provided herein are methods and compositions for modulating a microorganism's response to an antimicrobial agent. In one embodiment, the method comprises contacting the microorganism with an antimicrobial agent and bicarbonate. In one embodiment, provided herein are methods for treating a microbial infection comprising administering to a subject in need an effective amount of (i) bicarbonate and (ii) an antimicrobial agent. Also provided herein are methods of screening for antimicrobial compounds.

Bicarbonate as a potentiator for antimicrobial agents

Provided herein are methods and compositions useful for inhibiting microbe growth. The methods can comprise contacting the microbe with an antimicrobial agent and bicarbonate. In some embodiments, provided herein are methods for treating or preventing a microbial infection, comprising administering to a subject in need an effective amount of (i) bicarbonate and (ii) an antimicrobial agent.

Methods for inhibiting microbe growth

Therapeutic compositions and methods for treatment of late-onset Gaucher disease are described herein. The compositions comprise compounds having activity as pharmacological chaperones for mutant forms of the beta-glucocerebrosidase. Methods of treatment involve providing therapeutically effective amounts of such compositions to subjects in need thereof.

Method for enhancing folding and transport of misfolded glucocerebrosidase

Methods of treating Parkinson's disease

Methods of treating lysosomal storage disorders

Method of treating Gaucher disease

Method of treating gaucher disease

A method is provided for determining the activity of an enzyme which releases methylumbelliferone (MU) from an MU-containing substrate wherein the enzyme has a pH optimum below the pKa of MU comprising: contacting a sample suspected of containing the enzyme with the MU-containing substrate at a pH suitable for activity of the enzyme to allow release of MU by the enzyme; contacting the sample with light of a wavelength in the range of about 310 nm to about 350 nm; determining fluorescence produced by the released MU, thereby determining the activity of the enzyme. This real time method provides improved diagnostic methods, for example for diseases associated with an abnormal level of activity of a glycosidase. The real time assay also can be used to screen compounds for their ability to modulate enzyme activity using MU-containing substrates.

Real time methylumbelliferone-based assay

Growing community of inventors

Oakville, Canada

Eric Brown