Research
Kotra group is a multi-disciplinary group
adopting integrated chemical approaches to investigate and understand
biological problems of therapeutic interest. The research group expertise spans
computer
modeling, synthetic medicinal chemistry and biochemistry.
The research group is interested in exploring enzyme/receptor
structures, identifying underlying principles for ligand interactions,
designing chemical probe and intervention strategies, synthetic chemistry, and
confirming the biochemical mechanisms.
Our group collaborates widely with molecular biologists, structural
biologists and clinician-scientists to address questions beyond chemistry.
![MCDD01721_0000[1]](research_files/image006.gif){kind=small}
Research
Projects: Currently there are a number of exciting projects
in synthetic medicinal chemistry, computer modeling and
enzymology/thermodynamics. Current
ongoing projects are:
Organic/Medicinal Chemistry:
I.
Medicinal
chemistry and synthesis of structurally-novel pyrimidine, purine and other
modified nucleosides and nucleotides
II.
Synthesis
of novel small molecules mimicking protein-protein interactions
III.
Design
of focused libraries and structure optimization targeting diabetic neuropathy
Computer modeling:
I.
Understanding
ODCase and its inhibitors’ complexes using bioinformatics, molecular mechanics
and other computational tools
II.
Investigation
of protein-protein interactions using computer modeling and design of small
molecules mimetics
III.
Structure-based
design and lead hopping to generate novel chemical matter
Enzymology/thermodynamics:
I.
Enzymology
and biochemistry using novel techniques such as isothermal calorimetry, and
their applications in drug discovery
These projects have direct drug discovery
applications in the areas of cancer, infectious diseases (malaria, viral
infections, bacterial infection etc), diabetes and -related complications. Further details on the research projects can
be obtained by contacting Dr. Kotra.
Please see Publications section for latest publications from the
group.
Research Group
Accomplishments:
(i)
A new strategy
called fluoropeptidomimetics to inhibit proteases with a wide array of
therapeutic applications.
(ii)
Discovery
of new classes of nucleoside derivatives with applications in parasitic,
bacterial, RNA viral diseases as well as in cancer.
(iii)
Structure-based
design of small molecules mimicking insulin-insulin receptor interactions.
Discoveries from our group have entered into mouse efficacy studies in
two different therapeutic areas. Kotra
group enjoys excellent scientific collaborations with Prof. Emil Pai
(structural biology, University of Toronto), Dr. Kevin Kain (parasitology,
Toronto General Hospital), Dr. Chris Paige (cancer, Ontario Cancer Institute),
Prof. Dasantila Golemi-Kotra (protein chemistry, York University) and Prof.
Eleanor Fish (virology, University of Toronto).