A spectroscopic and molecular mechanics investigation on a series of AIB-based linear peptides and a peptide template, both containing tryptophan anda nitroxide derivative as probes

Linear Aib-based hexapeptides, of the general formula Ac-Toac-(Aib)(n)-Trp- (Aib)(r)-OtBu [T(Aib)(n)Trp], where n + r = 4, and Toac is a nitroxide spin -labeled C-alpha,C-alpha-disubstituted glycine, were investigated by steady -state and time-resolved fluorescence measurements in different solvent med ia. A related peptide, i.e., cyclo-{Orn-[(Aib(2))-Trp-(Aib)(2)-Z]-Asp-[(Aib )(2)-Toac-(Aib)(2)-OtBu]} [T-cyclo-Trp], was also studied by the same techn iques. It is a L-Orn, L-Asp diketopiperazine template, to which two Aib-bas ed chains are covalently attached each one containing one chromophore only, i.e., Trp or Toac. Whatever the soh ent, in the former ser ies of peptides quenching of the excited Tip exhibits three lifetime components and procee ds on a time scale from subnanoseconds to a few nanoseconds, while in the c ase of the template the same process occurs entirely on the nanoscale time scale, exhibiting two lifetimes only. The ir absorption spectral patterns s uggest that the backbone of the peptides examined is in the 3(10)-helical c onformation, as earlier determined by x-ray diffraction for T(Aib)(3)Trp in the crystal state. In all cases, the fluorescence results are satisfactori ly described by a dipole-dipole interaction mechanism, in which electronic energy transfer takes place from the excited Trp to Toac, provided the mutu al orientation between the fluorophore and Toac is taken into account. This implies that interconversion among conformational substates is slow on the time scale of the transfer process, allowing us to estimate the dynamics o f the process. Molecular mechanics calculations coupled with time decay dat a made it possible to build up the most probable structures of these peptid es in solution. (C) 2000 John Wiley & Sons, Inc.