Screening assays to identify compounds which modulate T1R associated taste modalities which eliminate false positives

A high throughput screening method for identifying compounds that putatively modulate sweet taste wherein such method reduces or eliminates “false positives”, the method comprising the steps of:

• (i) screening a thousand or more compounds in an assay that identifies compounds which specifically bind to or modulate the activity of a human T1R2/T1R3 heteromeric taste receptor or which modulate the binding or the activation of a human T1R2/T1R3 heteromeric taste receptor by another compound;
• (ii) further conducting a counter-screen using the identified putative human T1R2/T1R3 modulatory compounds identified from the thousand or more compounds screened in step (i), wherein said counter-screen detects whether said one or more identified putative human T1R2/T1R3 modulatory compounds specifically bind to or modulate the activity of a homomeric human T1R2 polypeptide or whether said one or more identified putative human T1R2/T1R3 modulatory compounds modulate the binding or the activation of a homomeric human T1R2 polypeptide by another human T1R2 agonist compound;
• and
• (iii) assessing the effect of the compounds which test positive in (i) and not in (ii) in human taste tests which assay the effect of said compounds on sweet taste, and producing variants or derivatives of the compounds that elicit or modulate sweet taste in said human taste tests and identifying those variants and derivatives which are suitable for use as flavorants in foods, beverages, medicaments or comestibles for human or animal consumption in the development of variants or derivatives, wherein said screening method does not include any other binding or functional assays using T1R taste receptor polypeptides and further does not screen using a cell which endogenously expresses said human T1R2/T1R3 taste receptor or a cell which endogenously expresses said homomeric human T1R2 polypeptide.