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KEYNOTE LECTURE PRESENTATION Open Access Pharmacology of fragrance: odors and GPCRs Stuart Firestein From 1st International Workshop on Odor Spaces Hannover, Germany. 4-7 September 2013 Odor receptors are the largest family of GPCRs on the planet. The identification of this large family of genes by Buck and Axel in 1991 showed that they have much in common with the other 450 or so GPCRs found in the mammalian genome. From this one might imagine that they can be profitably studied by using techniques devel- oped for standard GPCR pharmacology ligand screen- ing, structure activity relations, and a variety of modeling techniques. We have utilized synthetic chemistry to examine the structure-function activity of an odor recep- tor by utilizing a variety of synthetically designed ligands that demonstrate mechanisms for agonism, antagonism, partial agonism and reverse agonism. These analyses pro- vide a theoretical picture of the requirements for a bind- ing region within the receptor. The existence of a range of ligands from antagonists to high affinity agonists - for a given receptor must be taken into account when considering the type of upstream brain circuits that might be required to reduce the complex diversity of odor stimuli to the simpler categories of fragrance per- ception. In addition to these common principles of phar- macology that can be applied profitably to odor receptors we suggest that the techniques and strategies of medic- inal chemistry, normally targeted to a single specific receptor (e.g., dopamine, epinephrine, serotonin) can be modified for use in a large and varied receptor popula- tion. The med chem concept of bioisosterism, for exam- ple, may help to better define our thinking about broad and narrow tuning in receptors when applied to large numbers of receptors. Published: 16 April 2014 doi:10.1186/2044-7248-3-S1-K3 Cite this article as: Firestein: Pharmacology of fragrance: odors and GPCRs. Flavour 2014 3(Suppl 1):K3. Submit your next manuscript to BioMed Central and take full advantage of: Convenient online submission Thorough peer review No space constraints or color figure charges Immediate publication on acceptance Inclusion in PubMed, CAS, Scopus and Google Scholar Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Department of Biological Sciences, Columbia University, New York, NY 10027, USA Firestein Flavour 2014, 3(Suppl 1):K3 http://www.flavourjournal.com/content/3/S1/K3 © 2014 Firestein; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Page 1: Pharmacology of fragrance: odors and GPCRs

KEYNOTE LECTURE PRESENTATION Open Access

Pharmacology of fragrance: odors and GPCRsStuart Firestein

From 1st International Workshop on Odor SpacesHannover, Germany. 4-7 September 2013

Odor receptors are the largest family of GPCR’s on theplanet. The identification of this large family of genes byBuck and Axel in 1991 showed that they have much incommon with the other 450 or so GPCRs found in themammalian genome. From this one might imagine thatthey can be profitably studied by using techniques devel-oped for standard GPCR pharmacology – ligand screen-ing, structure activity relations, and a variety of modelingtechniques. We have utilized synthetic chemistry toexamine the structure-function activity of an odor recep-tor by utilizing a variety of synthetically designed ligandsthat demonstrate mechanisms for agonism, antagonism,partial agonism and reverse agonism. These analyses pro-vide a theoretical picture of the requirements for a bind-ing region within the receptor. The existence of a rangeof ligands – from antagonists to high affinity agonists -for a given receptor must be taken into account whenconsidering the type of upstream brain circuits thatmight be required to reduce the complex diversity ofodor stimuli to the simpler categories of fragrance per-ception. In addition to these common principles of phar-macology that can be applied profitably to odor receptorswe suggest that the techniques and strategies of medic-inal chemistry, normally targeted to a single specificreceptor (e.g., dopamine, epinephrine, serotonin) can bemodified for use in a large and varied receptor popula-tion. The med chem concept of bioisosterism, for exam-ple, may help to better define our thinking about broadand narrow tuning in receptors when applied to largenumbers of receptors.

Published: 16 April 2014

doi:10.1186/2044-7248-3-S1-K3Cite this article as: Firestein: Pharmacology of fragrance: odors andGPCRs. Flavour 2014 3(Suppl 1):K3.

Submit your next manuscript to BioMed Centraland take full advantage of:

• Convenient online submission

• Thorough peer review

• No space constraints or color figure charges

• Immediate publication on acceptance

• Inclusion in PubMed, CAS, Scopus and Google Scholar

• Research which is freely available for redistribution

Submit your manuscript at www.biomedcentral.com/submitDepartment of Biological Sciences, Columbia University, New York, NY 10027,

USA

Firestein Flavour 2014, 3(Suppl 1):K3http://www.flavourjournal.com/content/3/S1/K3

© 2014 Firestein; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.