Issue Date: July 25, 2016
Binding with deuterium
The cover story “The Deuterium Switcheroo” was very interesting (C&EN, July 4, page 32). I would like to note one minor, but not insignificant, error in the sentence that reads, “The hydrogen-deuterium switcheroo doesn’t change any of the drug’s other biological properties, such as its shape, size, or ability to bind its target.”
There is a substantial amount of evidence in the chemical literature to indicate that deuteration of a molecule does affect its noncovalent interactions with other molecules, such as binding to a target. This evidence was reviewed by me in 1999, and the subsequent review article, titled “Deuterium Isotope Effects on Noncovalent Interactions between Molecules” (Chem.-Biol. Interact. 1999, DOI: 10.1016/s0009-2797(98)00097-0), has been cited by more than 100 other authors in chemical journals, so the phenomenon is well-known.
It was my original hope that the phenomenon of isotope effects on noncovalent interactions could be developed for therapeutic benefit (see “Hypothesis: Slowing the Growth of β-Amyloid Fibrils with Deuterated Amino Acids” from the Wade Research Foundation), but most research has focused solely on the kinetic isotope effect described in the C&EN article.
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