The invention relates to biosensors for detecting odorants, especially a biosensor that mimics odorant detection by a mammal, for example, humans, dogs or cats. The field of the invention also related to the standardization of odors for scent, smell and taste using the biosensor of the invention, and the discovery of agonists, antagonists, and mixtures of odorants for creating new odors, masking odors, enhancing odors, and designing odors.

The present invention relates to a determination of antagonist effect of desired compound useful in the inhibition of activity of bradykinin receptors. Furthermore, the present invention provides an improved assay method to determine the efficacy of desired compounds by inhibiting the activity of bradykinin receptors. More specifically the present invention provides an improved assay method, wherein desired antagonistic effect of the compounds is determined by measuring intracellular calcium release.

The present invention relates to a screening method for materials that suppress the characteristic body odor of elderly people. The screening method of the present invention is designed such that test substances are screened with olfactory receptors responsive to substances responsible for the characteristic body odor of elderly people to select candidate substances for materials that suppress the characteristic body odor of elderly people, and this method comprises adding a test substance and a substance responsible for the characteristic body odor of elderly people to at least one olfactory receptor polypeptide selected from the group consisting of (a) OR2C1, OR2J2, OR4E2 and OR5P3, and (b) polypeptides which comprise an amino acid sequence sharing an identity of at least 80% with the amino acid sequence of any of the polypeptides in (a) and which are responsive to the substance responsible for the characteristic body odor of elderly people; measuring the response of the olfactory receptor polypeptide to the substance responsible for the characteristic body odor of elderly people; and identifying a test substance that suppresses the response of the olfactory receptor polypeptide on the basis of the measured response. Moreover, the present invention relates to a screening method for trans-2-nonenal odor suppressors and a screening method for trans-2-octenal odor suppressors.

The invention relates to a method for determining the ability of a molecule to modulate the activity of a G protein-coupled receptor (GPCR), said method comprising the following steps: a) introducing, into a first container:—a first membrane preparation bearing one or more GPCRs and one or more G protein(s),—a source of GDP or a source of GTP,—a first ligand of the alpha subunit of a G protein (Galpha protein) labelled with a first member of a pair of RET partners, and a second ligand of the Galpha protein labelled with a second member of the pair of RET partners, said ligands being able to specifically bind, either individually or in combination, to the empty Galpha protein or to the full Galpha protein; b) measuring the RET signal emitted in the first container; c) introducing (i) into a second container, the same reactants as in step a) and the molecule to be tested or (ii) into the first container, the molecule to be tested; d) measuring the RET signal emitted in the second container or in the first container obtained in step c); e) comparing the signals obtained in steps b) and d).

TABLE-US-00001 AA GPCR activation BB from “full” G to “empty” G form CC Agonist DD Format 1 EE Format 2 FF G.sub.empty GG Before activation HH After activation

The invention provides human AdipoR2 which is associated with the cardiovascular diseases, dermatological diseases, gastroenterological diseases, cancer, hematological diseases, respiratory diseases, inflammation, neurological diseases, urological diseases. The invention also provides assays for the identification of compounds useful in the treatment or prevention of cardiovascular diseases, dermatological diseases, gastroenterological diseases, cancer, hematological diseases, respiratory diseases, inflammation, neurological diseases, urological diseases. The invention also features compounds which bind to and/or activate or inhibit the activity of AdipoR2 as well as pharmaceutical compositions comprising such compounds.

Described are the discovery, synthesis and pharmacological characterization of δ-opioid receptor-selective positive allosteric modulators (δ PAMs). These δ PAMs may increase the affinity and/or efficacy of the orthosteric agonists leu-enkephalin and SNC80, as measured by β-arrestin recruitment and adenylyl cyclase inhibition. The compounds may be useful pharmacological tools to probe the molecular pharmacology of the δ receptor and to explore the therapeutic potential of δ PAMs in diseases such as chronic pain and depression.

The invention relates to cyclic peptide agonists that bind to the mu (morphine) opioid receptor and their use in the treatment of acute and/or chronic pain. Embodiments of the invention are directed to cyclic analogs of endomorphin. These peptide analogs exhibit decreased tolerance relative to morphine, increased solubility compared to similar tetrapeptide analogs, while maintaining favorable or improved therapeutic ratios of analgesia to side effects.

A protein-based probe for detecting the presence of one of two distinct states of a target membrane-associated molecule by means of polarization microscopy is disclosed. The probe contains an anchoring moiety consisting of at least one lipidated peptide and/or at least one transmembrane α-helical peptide, a peptide linker moiety having the length of at least 5 amino acids, wherein at least 50% of the amino acids forming the linker are selected from glycine, serine, and threonine, a fluorescent moiety, and an affinity binding moiety capable of binding the target membrane-associated molecule. The moieties are arranged in the order a-b-c-d or d-c-b-a in the direction from the N-terminus to the C-terminus. Methods of detecting presence or absence of the target molecule, detecting activated or inactive forms of the target molecule, and detecting the activation of the target molecule are also described.

An isolated antibody, comprising: a heavy chain variable domain (V.sub.H) that is at least 75% identical to the amino acid sequence of SEQ ID NO: 1; and a light chain variable domain (V.sub.L) that is at least 75% identical to the amino acid sequence of SEQ ID NO: 2; wherein the antibody binds specifically to human neurotensin receptor 1 (hNTSR1).

The present disclosure relates generally to methods and materials for the identification of compounds that modulate (e.g., enhance, agonize, or antagonize) G protein-coupled receptor (GPCRs), such as those involved in taste. Examples of such GPCR include the TAS1R proteins and the TAS2R proteins that are involved in sensing sweet taste. In certain aspects, the disclosure provides cell-based and label-free assays that use highly sensitive biosensors to detect candidate taste modulator compounds by their alteration of GPCR activity. In some embodiments, such cell-based and label-free assays may be used to detect changes in cell mass distribution, cell adhesion, or cell morphology, resulting from contact with a candidate taste modulator compound. In some embodiments, such assays detect GPCR activation with greatly improved sensitivity compared to conventional assay methods.