Biological Sciences
Biochemistry
The biochemistry group in the Merck Frosst Centre for Therapeutic Research develops the assays used to determine how new compounds interact with biological systems. There are two research strands: enzymes and receptors.
To study the interaction between enzymes, and substrates or inhibitors, the biochemists of Merck Frosst use state-of-the-art optical techniques.
For example, the Biochemistry group has characterized the enzymes involved in apoptosis (programmed cell death). Merck scientists discovered the first caspase, interleukin-1 beta converting enzyme. Biochemists at Kirkland have elucidated the role of caspases in slow degenerative neurological diseases. In a paper in Cell, the group described how these enzymes interact with beta amyloid precursor protein to damage neurons in Alzheimer's disease.
The search for inhibitors of the cysteine protease, cathepsin K, is another major initiative. By examining the mechanisms involved in bone resorption and how inhibitors interact in this system, scientists at Merck Frosst hope to find a novel approach for the treatment of osteoporosis.
To study the interaction between enzymes, and substrates or inhibitors, the biochemists of Merck Frosst use state-of-the-art optical techniques.
For example, the Biochemistry group has characterized the enzymes involved in apoptosis (programmed cell death). Merck scientists discovered the first caspase, interleukin-1 beta converting enzyme. Biochemists at Kirkland have elucidated the role of caspases in slow degenerative neurological diseases. In a paper in Cell, the group described how these enzymes interact with beta amyloid precursor protein to damage neurons in Alzheimer's disease.
The search for inhibitors of the cysteine protease, cathepsin K, is another major initiative. By examining the mechanisms involved in bone resorption and how inhibitors interact in this system, scientists at Merck Frosst hope to find a novel approach for the treatment of osteoporosis.
In addition to this work on enzymes, another major focus of the biochemistry group is G-protein coupled receptors (GPCRs), particularly the eicosanoid receptors. Receptor cDNA is cloned and then over-expressed in mammalian cell lines where affinity, dissociation and other binding parameters are evaluated with the assistance of robotic pipetting equipment. Functional assays and reporter gene technology are used to identify second messengers and to observe signalling mechanisms.
An on-going program to identify ligands of orphan GPCRs identified the cys-LT1 receptor for SINGULAIR® (montelukast sodium) (Nature 1999).
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