Fig. 2.

Ligand spectrum of OR51E1. a Molecular receptive field of OR51E1. Structurally related molecules were tested in luciferase reporter assays for their ability to activate heterologously expressed OR51E1, using nonanoic acid as a template. Effective ligands are shown in a green field; inactive compounds are in a blue field. Receptor-inhibiting substance is shown in a blue rectangle. The active analog approach identifies a mono carboxyl functional group as key feature for OR51E1 activation; alkyl side chain length can vary from C4 to C14; methyl substitutions are not tolerated at Cβ. Double bonds are tolerated at Cβ but affect negatively the activating property of the compound at Cκ (e.g., undecanoic acid: activating, 10-undecenoic acid: inactive). Aromatic functional groups are not tolerated. b Concentration–inhibition curve. Each response was normalized to the agonist nonanoic acid (200 µM) alone. The calculated IC₅₀ was 192 μM. The curve shift was significant at concentrations higher than 100 µM 2-ethylhexanoic acid (*p < 0.05). c Dose–response curves in the presence of OR51E1 antagonist. To determine receptor-inhibiting properties of compounds, OR51E1-expressing cells were co-stimulated with a rising concentration of nonanoic acid and a fixed concentration of 2-ethylhexanoic acid (400 µM). The mean of cellular responses was measured by luciferase reporter assays in four biological replicates and normalized to the positive control (forskolin). 2-ethylhexanoic acid acts as a competitive inhibitor on OR51E1. Significance was calculated by Student’s t test (*p < 0.05, **p < 0.01 and ***p < 0.001). Error bars represent the SEM