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High Throughput Receptor Screening Assays

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Abstract

The recent technical advances in functional expression of olfactory receptors (GlossaryTerm

OR

s) make full deorphanization of human OR repertoire a realistic objective. Such a global knowledge of the precise mechanisms of odorant/receptor pairings will represent a crucial step for the development of an accurate model of how human nose perceives its chemical environment. Beyond its interest for basic science, it will also lead to the development of industrial applications such as receptor-based odorant design, development of selective odor blockers or enhancers and represents therefore an interesting opportunity for players active in the field of flavors and fragrances. Here, we will describe and discuss a high-throughput screening approach that aims at the objective of human OR mass deorphanization. However, the completion of this ambitious task is not a prerequisite to the development of commercial applications. With the expanding number of deorphanized ORs, structure–activity relationship studies on OR responding to an odorant of interest has already started. Likewise, the use of the screening approach to identify either blockers for malodor-responding ORs or positive enhancers of fine fragrance-tuned ORs is underway. These different aspects will also be discussed. Finally, beyond the human ORs, other classes of human chemoreceptors for volatiles as well as animal chemoreceptors may also represent industrial opportunities that will be briefly reviewed.

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Abbreviations

\(\upmu{}\mathrm{M}\) :

micromolar

3-D:

three-dimensional

AMP:

adenosine monophosphate

cAMP:

cyclic adenosine monophosphate

CNG:

cyclic nucleotide gated

DMSO:

dimethyl sulfoxide

DNA:

deoxyribonucleic acid

EMEM:

Eagle’s modified essential medium

FDSS:

functional drug screening system

fMRI:

functional magnetic resonance imaging

GFP:

green fluorescent protein

GPCR:

G protein coupled receptor

HEK:

human embryonic kidney cell

HTS:

high-throughput screening

IBMX:

isobutyl methyl xanthine

OBP:

odor binding protein

ODR:

odorant response

OR:

olfactory receptor

PCR:

polymerase chain reaction

PLC:

phospholipase C

SAR:

structure–activity relationship

TAAR:

trace amine associated receptor

UV:

ultraviolet

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Acknowledgements

This work was supported by the Brussels Institute for Research and Innovation (InnovIRIS).

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Veithen, A., Philippeau, M., Chatelain, P. (2017). High Throughput Receptor Screening Assays. In: Buettner, A. (eds) Springer Handbook of Odor. Springer Handbooks. Springer, Cham. https://doi.org/10.1007/978-3-319-26932-0_22

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