Secondary structure of synthetic oligopeptides

The secondary structure of three hydrophobic peptides P2, PRMo and P4 was studied by a combination of Circular Dichroism (CD), Fourier Transform InfraRed (FTIR) and Photoinduced Electron Transfer (PET). These peptides were fluorescence labelled in the central part of the backbone and contained two modified glutamic acid residues (relative positions i, i+4): one conjugated with the fluorescence methoxynapththalene electron donor (DON) and the other with the piperidone electron acceptor (ACC). The three peptides were synthesised to study the length dependence of the switch between α-helix and the 310-helix conformations, previously observed for peptide PRM1 (Hungerford et al., Angew. Chem., Int. Ed. Engl., 1996, 35, 326-329). The CD and FTIR data indicated that peptides P2, PRMo and P4 adopt α-helical conformation in organic media in the temperature range studied and no conformational switch was detected. Furthermore, a mathematical correlation was observed in the PET data, questioning the agreement between CD and PET data initially observed for PRM1 (Hungerford et al., Angew. Chem., Int. Ed. Engl., 1996, 35, 326-329). The study of the peptide family was completed by 1D and 2D 1H-NMR study of a new peptide (P1) that had a similar sequence to PRM1 but contained two glutamic acid residues conjugated with a piperidine moiety. Delineation of hydrogen bonded NH groups in MeCN/DMSO and MeOH-d3 revealed a stable α-helix conformation for P1 in both media and proved the necessity of revising the conformational switch hypothesis suggested by Hungerford et al. A new technique, Raman Optical Activity, was proven useful in the study of peptide secondary structure in organic media by studying peptides P1 and the Ala-rich R1, whose helical structure were also characterised by CD and FTIR. Study of the fluorescence mechanism was performed on the model compounds and peptides in solution. The fluorescence steady state data proved Electron transfer (ET) as the mechanism responsible for the fluorescence quenching in our system, and that the quenching process was enhanced by insertion of the groups in the peptide sequence. (author)