Structural features of linear, homo-Aib-based peptides in solution: a spectroscopic and molecular mechanics investigation

In continuation of our studies on the determination of the structural featu res of functionalized peptides in solution by combining time-resolved fluor escence data and molecular mechanics results, the conformational properties of a series of linear, homo-Aib peptides in methanol (a structure-supporti ng solvent) were investigated. These compounds have the general formula P(A ib)(n)N, where Aib is alpha -aminoisobutyric acid, N is naphthalene and P i s the monomethylated protoporphyrin IX, the two latter chromophores being c ovalently attached to the peptide C- and N-termini, respectively, while n-3 , 6 and 9. According to H-1 NMR and IR spectra, the peptides investigated l argely populate a 3(10)-helical structure in CDCl3, which is also a structu re-supporting solvent. Both steady-state and time-resolved fluorescence mea surements show a strong quenching of the N emission that parallels an incre ase of the P fluorescence intensity, suggesting the occurrence of long-rang e energy transfer from N-1* to ground-state P. Comparison of quenching effi ciencies and lifetime pre-exponents with those obtained theoretically from the deepest energy minimum conformers is very satisfactory. The computed st ructures, built up by partially taking into account the solvent medium, exh ibit a rigid, highly compact arrangement, owing to both the 3(10)-helix con formation of the backbone chain and the very few peptide-to-chromophore cov alent linkages. As a result, only one or two stable conformations for each peptide were theoretically found, in full agreement with the time-resolved fluorescence data. Orientational effects between the probes must be taken i nto account for a correct interpretation of the fluorescence decay results, which implies that interconversion among conformational substates of the N linkages is slower than 10 ns, corresponding to the upper limit of the ene rgy transfer characteristic time.