TECHNICAL FIELD

The invention relates to a method for identifying compounds that can counteract malodours, notably malodours from sulfur odorants.

BACKGROUND ART

Humans perceive an immense variety of chemicals as having distinct odours. Odour perception initiates in the nose, where odorants are detected by a large family of olfactory receptors (ORs).

The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCRs) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals.

Volatile compounds of natural or artificial origin can be detected by a specific set of G-protein coupled receptors located in the respiratory epithelium. It has been proposed that one odorant is capable of activating multiple olfactory receptors (ORs) and that one OR is capable of detecting different odorants (NPL 1). The human genome contains ˜400 intact olfactory receptor genes belonging to two main classes. Class I, “fish-like receptors” ORs presumably detect water soluble odorants, whereas class II “tetrapod specific receptors” ORs are supposed to respond to airborne volatiles (NPL 2).

A mouse olfactory receptor was recently identified, which responds to (methylthio)methanethiol in heterologous cells (NPL 3).

Human body odour is generated from natural materials present on the skin surface and secretions from the sweat and sebaceous glands. These materials are converted to characteristic odourous compound through oxidative degradation or metabolism by skin microbes.

Human apocrine sweat gland secretions are known to produce a highly individual scent upon the action of skin flora that are present in high concentrations in the armpit.

Volatile steroids, aliphatic, branched and linear fatty acids have been reported as major contributors to human axillary malodour. 3-hydroxy-3-methyl-2-hexanoic acid was in particular found to originate from a glutamine conjugate present in axillary secretions (NPL 4).

Sulfur-containing compounds have also been found to be contributors of human axillary malodour (NPL 4; NPL 5). Sulfur-containing compounds have also been identified on worn laundry from the catabolism of L-methionine (NPL 6), and from urine (NPL 7).

Sulfur containing materials are also sometimes deliberately added to consumer or industrial products as active ingredients, for example thioglycolic acid or salts and cysteine for hair treatment products, and give the product an undesirable base odour that needs to be overcome.

CITATION LIST

Non Patent Literature

[NPL 1]Malnic B, Hirono J, Sato T, Buck L B. “Combinatorial receptor codes for odors.” Cell 1999 96(5):713-23[NPL 2]Glusman G, Bahar A, Sharon D, Pilpel Y, White J, Lancet D. “The olfactory receptor gene superfamily: data mining, classification, and nomenclature. Mamm.” Genome 2000 11(11):1016-23[NPL 3]Duan X, Block E, Li Z, Connelly T, Zhang J, Huang Z, Su X, Pan Y, Wu L, Chi Q, Thomas S, Zhang S, Ma M, Matsunami H, Chen G Q, Zhuang H. “Crucial role of copper in detection of metal-coordinating odorants.” Proc. Natl. Acad. Sci. USA 2012 109(9):3492-7[NPL 4]Troccaz. “The biosynthetic pathway of sulfur-containing molecules in Human Axillary Malodor: from precursors to odorous volatiles.” These de doctorat: Univ. Geneve, 2009, no. Sc. 4102 (https://archive-ouverte.unige.ch/unige:4563)[NPL 5]Natsch A, Schmid J, Flachsmann F. “Identification of odiferous sulfanylalkanols in human axilla secretions and their formation through cleavage of cysteine precursors by a C-S lyase isolated from axilla bacteria.” Chemistry & Biodiversity 2004 1(7):1058-1072[NPL 6]Denawaka C, Fowlis, I, Dean J. “Source, impact and removal of malodour from soiled clothing.” Journal of Chromatography A 2016 (1438): 216-225[NPL 7]Troccaz M, Niclass Y, Anziani P, Starkenmann C. “The influence of thermal reaction and microbial transformation on the odour of human urine.” Flavour & Fragrance Journal 2013 (28): 200-211.[NPL 8]Li S, Ahmed L, Zhang R, Pan Y, Matsunami H, Burger J L, Block E, Batista V S, Zhuang H. “Smelling sulfur: copper and silver regulate the response of human odorant receptor OR2T11 to low-molecular-weight thiols.” Journal of the American Chemical Society 2016 (doi:10.1021/jacs6b06983)[NPL 9]Noe F, Polster J, Geithe C, Kotthoff M, Schieberle P, Krautwurst D. OR2M3: “A highly specific and narrowly tuned human odorant receptor for the sensitive detection of onion key food odorant 3-mercapto-2-methylpentan-1-ol.” Chemical Sciences 2016, 00:1-16 (doi:10.1093/chemse/bjw118)[NPL 10]Saito H, Kubota M, Roberts R W, Chi Q, Matsunami H. “RTP family members induce functional expression of mammalian odorant receptors.” Cell 2004 119(5):679-91[NPL 11]Von Dannecker L E, Mercadante A F, Malnic B. “Ric-8B, an olfactory putative GTP exchange factor, amplifies signal transduction through the olfactory-specific G-protein Galphaolf.” J Neurosci. 2005 Apr. 13; 25(15):3793-800[NPL 12]Von Dannecker L E, Mercadante A F, Malnic B. “Ric-8B promotes functional expression of odorant receptors.” Proc. Natl. Acad. Sci. USA 2006 103(24):9310-4[NPL 13]Bufe B, Hofmann T, Krautwurst D, Raguse J D, Meyerhof W. “The human TAS2R16 receptor mediates bitter taste in response to beta-glucopyranosides.” Nat. Genet. 2002 32(3):397-401

SUMMARY OF INVENTION

Technical Problem

It has now been found that a human olfactory receptor, OR4E2, responds to sulfur odorants. Accordingly the use of this polypeptide is contemplated for identifying compounds which can counteract the perception of malodour from sulfur odorants.

Solution to Problem

In one aspect, the invention relates to a method for determining whether a test compound can counteract the perceived (smelt) malodour from a sulfur odorant, the method comprising the steps of:

a) contacting the OR4E2 polypeptide with a sulfur odorant, in the presence and in the absence of the test compound under conditions permitting the binding of said sulfur odorant to OR4E2 or permitting the activation of OR4E2 by said sulfur odorant; and

b) comparing the binding of OR4E2 to said sulfur odorant, or the activity of OR4E2, in the presence and in the absence of the test compound, wherein an inhibition of the binding or a decrease in activity in the presence of the test compound, relative to the binding or activity in the absence of the test compound, identifies the test compound as a compound that can counteract the perceived malodour from the sulfur odorant.

In another aspect, the invention relates to an anti-malodour composition comprising a compound identified by the above-mentioned method.

In another aspect, the invention relates to household, laundry, personal care, animal care or industrial products comprising a compound identified by the above-mentioned method, or an anti-malodour composition as defined above.

In another aspect, the present invention relates to the use of the OR4E2 polypeptide for identifying a compound that can counteract the perceived malodour from a sulfur odorant.

Advantageous Effects of Invention

In the present invention, a method for identifying compounds that can counteract malodours, notably malodours from sulfur odorants can be provided.

