Ligands for odor receptors and olfactory neurons

Abstract

The disclosure provides compounds useful as insect repellents and compositions comprising such repellents. The disclosure further provides insect traps and method for identifying ligands and cognates for biological molecules.

1 - 41 . (canceled) 
     
     
         42 . A composition, comprising one or more compounds selected from Table 9, Table 10, and any combination thereof, in a trap, a cream, a lotion, a spray, a dust, a vapor emitter, a candle, an oil, a wicked apparatus, a fan, a vaporizer, a perfume, a cologne, a fragrance, a deodorant, a masking agent, or any combination thereof. 
     
     
         43 . The composition of  claim 42 , wherein the one or more compounds is an arthropod repellant or attractant. 
     
     
         44 . The composition of  claim 42 , wherein the one or more compounds is in a trap, and wherein the one or more compounds lures insects into the trap by activating odor receptors, affecting insect mating behavior, or a combination thereof. 
     
     
         45 . The composition of  claim 44 , wherein the trap is suction-based, light-based, or electric current-based. 
     
     
         46 . The composition of  claim 44 , wherein the trap has an entrance, and wherein the composition further comprises:
 a liquid source, wherein the liquid source evaporates to form vapors within or near the entrance of the trap.   
     
     
         47 . A method of identifying a ligand for a biological molecule, comprising:
 a) providing a training set comprising a plurality of activating odorants;   b) identifying a plurality of descriptors from the plurality of activating odorants in the training set;   c) using a Sequential Forward Selection (SFS) descriptor selection algorithm to provide a descriptor subset from the plurality of descriptors identified in step (b);   d) identifying a set of putative ligands from a test set of compounds by ranking the compounds in the test set based on distance from each activating odorant calculated using the descriptor subset from step (c); and   e) testing each putative ligand in a biological assay, wherein the biological assay comprises the biological molecule, and wherein a change in activity of the biological molecule in the presence of a putative ligand compared to the activity of the biological molecule in the absence of the putative ligand is indicative of a ligand that interacts with the biological molecule.   
     
     
         48 . The method of  claim 47 , wherein the biological molecule is an odor receptor or a gustatory receptor. 
     
     
         49 . The method of  claim 47 , wherein the use of the SFS descriptor selection algorithm increases a correlation between the compound-by-compound activity and the compound-by-compound descriptor distance matrix for each activating odorant in the training set. 
     
     
         50 . The method of  claim 47 , wherein the plurality of descriptors in step (b) are selected from the group consisting of distance metrics, descriptor sets, activity thresholds, and any combination thereof. 
     
     
         51 . The method of  claim 50 , wherein the distance metrics are selected from the group consisting of Euclidean coefficients, Spearman coefficients, Pearson coefficients, and any combination thereof. 
     
     
         52 . The method of  claim 50 , wherein the descriptor sets are selected from the group consisting of a Dragon descriptor set, a Cerius2 descriptor set, or a combined Drgran/Cerius2 descriptor set. 
     
     
         53 . The method of  claim 50 , wherein the activity thresholds are based on activity-based cut offs. 
     
     
         54 . The method of  claim 47 , wherein the identifying of the set of putative ligands in step (c) comprises selecting putative ligands each having a Euclidian distance of about 0.001 to 6.60 from the compounds in the training set. 
     
     
         55 . The method of  claim 47 , wherein the identifying of the set of putative ligands in step (c) comprises selecting putative ligands falling within about 1% of the compounds in the training set. 
     
     
         56 . The method of  claim 47 , wherein one or more of the putative ligands identified in step (c) binds to a CO 2  receptor, and wherein the one or more putative ligands are selected from Table 9, Table 10, or a combination thereof. 
     
     
         57 . The method of  claim 47 , wherein the plurality of descriptors in step (b) are selected from Table 7, Table 8, or any combination thereof. 
     
     
         58 . The method of  claim 47 , wherein the biological assay in step (e) measures a change in spike frequency, fluorescence intensity, or binding affinity.