Applying medicinal chemistry strategies to understand odorant discrimination

Affordable Access

Download Read

Applying medicinal chemistry strategies to understand odorant discrimination

Authors
  • Erwan Poivet
  • Zita Peterlin
  • Narmin Tahirova
  • Lu Xu
  • Clara Altomare
  • Anne Paria
  • Dong-Jing Zou
  • Stuart Firestein1
Type
Published Article
Journal
Nature Communications
Publisher
Springer Nature
Publication Date
Apr 03, 2016
Volume
7
Identifiers
DOI: 10.1038/ncomms11157
Source
MyScienceWork
License
Green

Abstract

Associating an odorant's chemical structure with its percept is a long-standing challenge. One hindrance may come from the adoption of the organic chemistry scheme of molecular description and classification. Chemists classify molecules according to characteristics that are useful in synthesis or isolation, but which may be of little importance to a biological sensory system. Accordingly, we look to medicinal chemistry, which emphasizes biological function over chemical form, in an attempt to discern which among the many molecular features are most important for odour discrimination. Here we use medicinal chemistry concepts to assemble a panel of molecules to test how heteroaromatic ring substitution of the benzene ring will change the odour percept of acetophenone. This work allows us to describe an extensive rule in odorant detection by mammalian olfactory receptors. Whereas organic chemistry would have predicted the ring size and composition to be key features, our work reveals that the topological polar surface area is the key feature for the discrimination of these odorants.

Report this publication

Statistics

Seen 625 times
Downloaded <100 times