On Chaperones

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 m

David Clarke

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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

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