NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPIC ANALYSIS OF THE SELECTIVE COMPLEXATION OF THE CIS AND TRANS ISOMERS OF PHENYLALANYLPROLINE BY BETA-CYCLODEXTRIN

Nuclear magnetic resonance (NMR) spectroscopy was used to examine the effect of beta-cyclodextrin inclusion complex formation on the cis-tra ns equilibrium constant of phenylalanylproline, Phe-Pro. The pK(a) val ues of the ionizable groups of Phe-Pro have been determined in solutio ns containing equimolar ratios of the peptide and beta-cyclodextrin. C omparison of these values with acidity constants of the free peptide s uggest a hydrogen bond between beta-cyclodextrin and the cis isomer ca rboxylate group that is not observed for the trans isomer. Diffusion c oefficients for the cis and trans isomers of Phe-Pro in aqueous and in beta-cyclodextrin solution have been measured using pulsed-field grad ient NMR spectroscopy. Diffusion ordered NMR spectroscopy (DOSY) was u sed to selectively measure the diffusion coefficients of beta-cyclodex trin and both isomers of Phe-Pro. The preferential formation of the be ta-cyclodextrin inclusion complex with cis Phe-Pro was observed in the DOSY spectra and formation constants for this complex calculated.