Influence of solvents and leucine configuration at position 5 on tryptophan fluorescence in cyclic enkephalin analogues

The fluorescence decay of tryptophan is a sensitive indicator of its local environment within a peptide or protein. In this study we carried our fluor escence measurements of the tryptophan residue of cyclic enkephalin analogu es of a general formula X-c[D-Dab(2)-Gly(3)-Trp(4)-Y-5] where X = Cbz or H and Y = D- or L-Leu, in four solvents [water, methanol, acetonitrile, and d imethyl sulfoxide (DMSO)]. An analysis of the tryptophan fluorescence decay s using a discrete-exponential model indicates that tryptophan fluorescence decay can be described by a double exponential function in all solvents st udied. Lifetime distribution analysis yields a bimodal distribution in prot ic solvents (water and methanol), whereas an asymmetric, unimodal distribut ion in an aprotic solvent (DMSO) and uni- or bimodal distributions in aceto nitrile solution, depending on leucine configuration. The data are interpre ted in terms of the rotamer model, in which the modality and the relative p roportions of the lifetime components are related to the population distrib ution of tryptophan chi (1) rotamers about the C-alpha-C-beta bond. The chi rality of the Leu(5) residue and solvent properties affect the local enviro nment of the tryptophan residue and therefore influence the distribution of side-chain rotamers. These results are consistent with the results of theo retical conformational calculations. (C) 2001 John Wiley & Sons, Inc. Biopo lymers 58: 447-457, 2001.