On Chaperones

Your article, "Chaperones to the Rescue,"1 implied that the use of specific compounds (agonists, antagonists, substrates, or modulators) as chaperones to rescue misfolded proteins is a novel concept. To set the record straight, we draw your attention to the paper where it was first reported in 1997 that specific substrates and modulators could be used as a strategy to prevent protein misfolding in P-glycoprotein.2 These specific chaperones rescued misfolded proteins that had mutations throughout the molecule. We subsequently reported that the chaperones correct the folding defects by inducing superfolding/proper folding of the molecule by occupying the drug-binding site3 and promoting transmembrane domain interactions.4

David M. Clarke, Professor
Departments of Medicine and Biochemistry
University of Toronto
Toronto, Ontario M5S 1A8

1. S. Bunk, "Chaperones to the rescue," The Scientist, 16[22]:21-3, Nov. 12, 2002.

2. T.W. Loo, D.M. Clarke, "Correction of defective protein...

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