Research

Medicinal and pharmaceutical chemistry, green chemistry and biochemistry

Our research takes advantage of chemical tools to study and manipulate biological systems. We are especially interested in antibiotic resistance, enzymology and biocatalysis (towards green chemistry).

The Auclair research group has expertise in synthesis, medicinal chemistry, enzymology, mechanoenzymatic processes, biocatalysis, as well as protein purification, expression and engineering (including bioconjugation). The main goal of our research is to understand how enzymes work and how they can be harnessed or perturbed, especially for pharmaceutically relevant proteins such as antibiotic targets, resistance-causing enzymes, drug activation and drug metabolism. Results of these studies have implications in fields as varied as medicine, biotechnology, industrial processing, agriculture and food science.

Current projects fall under three areas:

1) Antibiotics and antibiotic resistance

2) Biocatalysis

3) Enzymology

1) Antibiotics and Antibiotic Resistance

Antibiotics are some of the pharmaceutical agents that have improved human life expectancy the most, yet they have one of the shortest utility lifespan of all drugs. By Darwinian selection and horizontal transfer, bacteria eventually develop resistance to all antibacterial agents, and as a result, antibiotic resistance is currently one of the most rapidly spreading health threats worldwide.

The strategies pursued in my group to overcome antibiotic resistance include (more recent is last):

1) Design inhibitors of antibiotic resistance. In particular, we have focused on aminoglycoside resistance

2) Discover new antibacterial and antiplasmodial (antimalarials) agents. Our efforts are mainly focused on pantothenamide analogs.

3) Look for compounds able to resensitize bacteria to the host immune defenses, a strategy which we have coined "bacterio-modulation". Our current strategy is to look for inhibitors of itaconate degradation as a means of resensitizing intracellular bacteria to itaconate produced by phagocytes.

For all three strategies, the group often takes advantage of the coenzyme A biosynthetic pathway to activate our molecules selectively within bacteria or parasites.

1) Biocatalysis

The strategies pursued in my group to enhance biocatalysis include (more recent is last):

1) Use of chemical auxiliaries to control and predict product formation by enzymes.

2) Bioconjugate allosteric effectors to enzymes to improve their activity.

3) Develop new solvent-free, mechano-enzymatic processed.


3) Enzymology

The enzymes of interest include:

1) P450 enzymes (P450s or CYPs)

2) Coenzyme A biosynthetic enzymes

3) Enzymes involved in antibiotic resistance or that are potential targets for the development of new treatments for infections.

We have a special interest for enzyme allostery and cooperativity.

 


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