MADISON - Trying a new approach to controlling the process of inflammation, scientists have forged a new class of synthetic molecules that offer a new strategy for treating pain, swelling and the other hallmarks of injury or illness.
Writing this week (March 5) in the scientific journal Nature, University of Wisconsin-Madison chemist Laura L. Kiessling describes a new family of compounds that packs a novel one-two punch that effectively inhibits the cellular processes that cause us pain.
Inflammation is the body's response to irritation, infection or injury. It begins at the level of the cell when, in response to an injury or irritation, white blood cells in the bloodstream begin to stick to the cells lining the blood vessel wall. The end result of this process is inflammation and pain.
The cells stick together with the aid of a protein called L-selectin that, with many other proteins, populates the surface of cells.
"L-selectin helps mediate an inflammatory response by binding to the carbohydrate groups attached to protein molecules on the surface of an opposing cell," said Kiessling. "The many copies of L-selectin on the white blood cell surface bind with the many copies of the L-selectin-binding protein on the blood vessel, much like fingers fitting into a glove. The inflammatory response depends on the cells sticking together."
The traditional approach to controlling inflammation, through popular over-the-counter drugs such as ibuprofen, is to block events inside the cell. The synthetic molecules in Kiessling's approach act as inhibitors on the outside of the cell, attaching themselves to a L-selectin proteins and preventing the cell from linking with an opposing cell.
But synthetic molecules that only inhibit cells from linking up have to compete
with the natural cell surface proteins involved in the cell-docking process, and
they don't always win. The process is also reversible. The synthetic molecules,
for example, can slip off the
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Contact: Laura L. Kiessling
kiessling@chem.wisc.edu
608-262-0541
University of Wisconsin-Madison
4-Mar-1998