Polydepsipeptides. A systematic investigation of guest-host effects

A series of tert-butyloxycarbonyl (Boc)-protected oligoglutamates with the general formula Boc-[L-Glu(OMe)]n-OMe (OMe, methoxy) (n = 2–7) was modified by substituting one Glu(OMe) residue with a lactic acid (Lac) moiety. The CD spectrum of each compound was recorded in TFE at a concentration of approximately 10−3 mol/l, and various difference spectra were analysed by spectral deconvolution. The fitting of the difference CD curves in the Boc-[L-Glu(OMe)]n-OMe series clearly indicates that even though the conformation of all the peptides is considered to be random, the actual conformations visited by the different oligomers are not the same, as demonstrated by the different contribution of the dipole coupling. A much bigger change is seen going from the trimer to the tetramer than from the tetramer to the pentamer, suggesting that three consecutive amide groups are critical for the development of sizable dipole coupling effects. The difference spectrum [Glu6 — Glu5] clearly indicates that even the hexapeptide probes α-helical conformations. The intrinsic effect of the ester substitution on the CD spectrum of a random coiled peptide is evident from this study: a weak contribution in the n-π* region and a definite disruption of amide π-π* dipole couplings. The next step would be to apply this approach to polymers in which both an intrinsic and a conformational effect of the ester are possible.