Combined effect of the ΔPhe or ΔAla residue and the p‐nitroanilide group on a didehydropeptides conformation

Abstract

Two series of dehydropeptides of the general formulae Boc-Gly-X-Phe-p-NA, Boc-Gly-Gly-X-Phe-p-NA, Gly-X-Gly-Phe-p-NA.TFA, and Boc-Gly-X-Gly-Phe-p-NA, with X = Delta(Z)Phe and DeltaAla, were studied with NMR in DMSO and CDCl(3)-DMSO, and with CD in MeOH, MeCN, and TFE. The NMR spectra measured in DMSO suggest that peptides with the DeltaPhe residue next to Phe are folded whereas peptides with Gly between DeltaPhe and Phe are less ordered. NMR spectra of DeltaAla-containing peptides indicate that these peptides are flexible and their conformational equilibria are populated by many different conformations. The CD spectra show that conformational properties of the peptides studied are distinctly influenced by a mutual position of the dehydroamino acid residue and the p-NA group. They indicate that all dehydropeptides with the DeltaPhe residue, Boc-Gly-DeltaAla-Phe-p-NA, and Boc-Gly-Gly-DeltaAla-Phe-p-NA adopt ordered conformations in all solvents studied, presumably of the beta-turn type. The last two peptides exhibit surprising chiroptical properties. Their spectra show exciton coupling-like couplets in the region of the p-NA group absorption. This shape of CD spectra suggests a rigid, chiral conformation with a fixed disposition of the p-NA group. The CD spectra indicate that Boc-Gly-DeltaAla-Gly-Phe-p-NA and Gly-DeltaAla-Gly-Phe-p-NA.TFA are unordered, independently of the solvent.

Effect of the ΔPhe residue configuration on a didehydropeptides conformation: A combined CD and NMR study

“…2) in the near-UV in MeOH, TFE, and MeCN show that the peptide adopts the type II β-turn conformation at the Gly 1 and ∆ Z Phe 2 residues, stabilized by the intramolecular hydrogen bond between the amide proton of Gly 3 and the carbonyl oxygen of the Boc group. 18 The presence of such a conformation is consistent with the NMR studies which show that the Gly 3 amide proton is involved in a hydrogen bond (Table II) and by the conformational calculations (Table V). The analogous reasoning as in the case of Z-OMe indicates that there is another β-turn, either at the ∆ Z Phe 2 and Gly 3 or Gly 3 and Phe 4 residues, stabilized by the corresponding 4→1 hydrogen bond.…”

“…It has been found that in the solid state a ∆Phe residue of the Z configuration induces β-turns in short sequences [2][3][4][5][6] and a 3 10 -helix in longer ones or peptides with more than one dehydro residue. 4,[7][8][9][10][11][12][13][14][15][16][17][18][19] Similar conformational properties of ∆ Z Phe have been observed in solution by NMR 8,11,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] and CD, 18,19,[27][28][29][30][31][32][33][34][35][36]…”

“…The peptides contain a ∆Phe residue which gives a large CD band in that region, at about 280 nm, which is very sensitive to a dehydropeptide conformation. 18,19,[27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] Thus, this residue is a very good conformational probe in the studies on dehydropeptides. Moreover, Z-p-NA and E-p-NA contain the p-NA group which has been also found to be a useful tool in the conformational studies on peptides.…”

“…35,61 In the case of Z-p-NA and E-p-NA, the ∆Phe residue band at 280 nm is overlapped by a charge-transfer band of the p-NA group at 315 nm. 18 The spectra of Z-p-NA and E-p-NA are very similar. They show a band at 286 and 289 nm, respectively, with a shoulder at about 325 nm which is quite distinct for Z-p-NA and poorly visible for E-p-NA.…”

Conformational studies of hexapeptides containing two dehydroamino acid residues in positions 2 and 5 in peptide chain

“…This is strongly dependent on the peptide conformation and therefore very useful in this kind of conformational studies. 21 The CD spectra obtained in three solvents for peptides no. 1 and no.…”