Chiral Recognition of Diketopiperazine Containing Proline Residues by (-)-Epigallocatechin-3-O-gallate in Water.

The stoichiometry and precipitate yield of a complex of (-)-epigallocatechin-3-O-gallate (EGCg) and cyclo(Pro-Xxx) (Xxx = phenylalanine (Phe), tyrosine (Tyr)) were evaluated using integrated values of their proton signals by quantitative H-NMR (q NMR). It was determined to be a 1 : 1 complex of EGCg and cyclo(Pro-Xxx). The change in the chemical shift value of proton signals of cyclo(Pro-Xxx) in H-NMR spectra by adding standard amounts of EGCg was investigated. Differences in chemical shift values of H, H, H, H, H, and H proton signals between cyclo(L-Pro-L-Phe) and cyclo(D-Pro-D-Phe), and those of H, H, H, H, H, H, and H proton signals between cyclo(L-Pro-L-Tyr) and cyclo(D-Pro-D-Tyr) were observed as a significant difference at 54 mmol/L of EGCg. It was found that their chirality was clearly recognized by EGCg. The significant difference in the change of the chemical shift value of H proton signals between cyclo(L-Pro-L-Xxx) and cyclo(D-Pro-D-Xxx) was the largest, and the difference was considered to have resulted from the difference in the ratio of extended conformer in equilibrium between folded and extended conformers. Such a significant difference in change values between cyclo(L-Pro-D-Xxx) and cyclo(D-Pro-L-Xxx) was not observed due to a rigid intramolecular CH-π interaction. EGCg did not clearly recognize the chirality of cyclo(L-Pro-D-Xxx) and cyclo(D-Pro-L-Xxx).