Fifty years of smelling sulfur: From the chemistry of garlic to the molecular basis for olfaction

GRAPHICAL ABSTRACT

ABSTRACT

The striking difference in odor threshold of low molecular weight thiols compared to analogous alcohols has been investigated by isolation and study of human olfactory receptors responsive to these thiols. It has been discovered that human thiol receptor OR2T11 responds specifically to gas odorants ethanethiol and 2-methyl-2-propanethiol, as well as to related low molecular weight thiols, and requires ionic copper for its robust activation. When OR2T11 is screened against a series of alcohols, thiols, sulfides and metal-coordinating ligands, it responds, with enhancement by copper, to four-membered cyclic sulfide thietane, to one- to four-carbon straight-, branched-chain and five-carbon branched-chain thiols, and to the mouse semiochemical CH₃SCH₂SH and derivatives, but not to longer chain thiols, suggesting compact receptor dimensions. Alcohols and hydrogen sulfide are unreactive.

KEYWORDS:

• Garlic
• thiols
• olfaction
• copper
• olfactory receptors

Acknowledgments

I gratefully thank my collaborators whose names appear in my coauthored publications given as references.

Funding

Support from the National Science Foundation (CHE-1265679) and the National Institutes of Health (5R01 DC014423-02 subaward) is gratefully acknowledged.