Modulation of chemosensory receptors and ligands associated therewith

A method of screening for a candidate of a chemosensory receptor ligand modifier comprising

• determining whether a test entity is suitable to interact with a chemosensory receptor via a first interacting site within the Venus flytrap domain of the chemosensory receptor,
• wherein the first interacting site is identified in light of a second interacting site identified based on the interaction between a chemosensory receptor ligand and the chemosensory receptor.

A method of screening for a candidate of a chemosensory receptor modifier comprising

• determining whether a test entity is suitable to interact with a chemosensory receptor via an interacting site within the Venus flytrap domain of the chemosensory receptor,
• wherein the interacting site includes an interacting residue selected from the group consisting of D147, S148, T149, N150, A170, A171, S172, S173, D192, N195, D218, Y220, S276, R277, E301, and A302 of a human T1R1 and a combination thereof, and
• wherein a test entity suitable to interact with the interacting site of the chemosensory receptor is indicative of a candidate of a chemosensory receptor modifier.

A method of modulating the activity of a chemosensory receptor ligand comprising contacting a chemosensory receptor ligand modifier with a cell containing T1R1 Venus flytrap domain in the presence of a chemosensory receptor ligand, wherein the chemosensory receptor ligand modifier interacts with an interacting site of the chemosensory receptor.

A chemosensory receptor ligand modifier, wherein in the presence of a chemosensory receptor ligand it interacts with T1R1 Venus flytrap domain via at least three interacting residues selected from the group consisting of L46, H47, S48, G49, C50, L51, S67, F68, N69, E70, H71, C106, S107, D108, D147, S148, T149, N150, R151, Y169, A170, A171, S172, S173, D192, N195, D218, Y220, S276, R277, E301, A302, F247, S248, S275, S276, R277, Q278, L279, A280, R281, V282, F283, F284, E285, E301, A302, W303, S306, R307, H308, I309, T310, G311, V312, P313, R317, K354, W357, K377, K379, M383, and S385 of a human T1R1.

A method of treating a condition associated with a chemosensory receptor comprising administering to a subject in need of such treatment an effective amount of an entity selected from the group consisting of a chemosensory receptor modifier, chemosensory receptor ligand modifier, and a combination thereof, wherein the entity interacts with an interacting site of the chemosensory receptor.