New chemistry clicks

A new method for tracking modified lipids in living cells is described online this week in Nature Chemical Biology. This robust technology, like its related chemical reaction ― called 'click' chemistry ― could provide a generalizable platform for studying any cellular process, such as protein functions and modifications.

The most famous example of click chemistry is the linkage of a triple bond, or alkyne, with three nitrogens, or an azide, to create a 5-membered ring. This reaction is used to attach fluorescent labels or other tagging agents to a variety of cellular molecules, which can then be easily visualized and studied. However, this is a permanent modification, making it harder to tell what the true structure or function of the biological target is.

Alex Brown and colleagues use cobalt molecules to bind alkynes that have been inserted in long lipid tails. The reaction is as specific as the click companion, but reversible, so the lipids attached to cobalt can be extracted from cells, but then characterized normally. As in the lab, alkynes can be inserted in a large number of molecules without causing functional changes; this technique should expand the ability of chemists and biologists to better understanding cellular function.