Preferred conformations of protected homo-oligo-L-glutamate peptides in CDCl3 and CDCl3/TFA mixtures

A conformational analysis of protected glutamate homo-oligopeptides Z-Glu(OEt)]_n-OEt (n = 2–7) was carried out in chloroform solution using high-resolution ¹H-nmr spectroscopy. At dilute peptide concentrations, the backbone NH and α-CH resonances are well resolved and can be assigned by combining extensive homonuclear decoupling experiments with data for co-oligopeptide derivatives. The structure of these peptides in solution was then assessed using information from chemical shifts, coupling constants, temperature coefficients, and titration of each oligomer with trifluoroacetic acid (TFA). The di- and tripeptides are found to be in disordered forms in deuterochloroform (CDCl₃) and CDCl₃/TFA mixtures. The tetrapeptide exhibits a folded structure with intramolecular hydrogen bonding at Glu² in CDCl₃ and undergoes a transition to increasingly disordered forms as TFA is added. The pentamer to heptamer show a folded structure with a strong intramolecular hydrogen bond at Glu² and a weaker hydrogen bond at Glu³, which are disrupted as these peptides go to random coils at high TFA/CDCl₃ ratios. In addition, the N-terminal portions of these glutamate peptides appear to be involved in side chain–main chain interactions. The results support the hypothesis that protected linear homo-oligopeptides may possess two or more segments of conformation with intramolecular folding preferred near the N-terminal portion.