A spectroscopic and molecular modeling study on novel pseudopeptides exhibiting biological activity

Italy A series of pseudopeptides, containing two fluorophores, such as naph thalene (N) and indole (I), and exhibiting interesting biological activity as tachykinin receptor antagonists, were investigated by electronic absorpt ion, CD and steady-state fluorescence experiments. In polar solvents (e.g. methanol), bioactivity is coupled with a stacked, charge-separated complex between I and N, the amount of which depends on the stereochemical features and conformational mobility of the central scaffold in the molecules exami ned. This agrees with the idea that dipolar charged, spatially close, aroma tic moieties are important topochemical elements in the Italy mechanism of action of these receptor antagonists. Molecular mechanics calculations allo wed us to build up hypothetical, low-energy conformations of a few represen tative pseudopeptides, whose structural features are consistent with the ex perimental findings.