Conformational studies on resiniferatoxin (RTX), an ultrapotent vanilloid agonist Original Research Article

In polar solution, NOE studies show a pronounced clustering of the aromatic moieties (9,13,14-phenylacetate orthoester and 20-homovanillate) of the ultrapotent vanilloid agonist resiniferatoxin (RTX). This clustering is absent in nonpolar solution. Low energy clustered structures from molecular dynamics simulations account for the observed NOEs. These results suggest that the phenylorthoacetate moiety can assist the attainment of specific alignments between the terpenoid core and the vanillyl moiety, possibly preorganizing them for ideal receptor binding.