Stabilization of Neutral NH2-R-COOH Form of the Antihypertensive Peptides L-Valyl-L-Prolyl-L-Proline and L-Isoleucyl-L-Prolyl-L-Proline

Spectroscopic and structural elucidation of the peptides (L)-Valyl-(L)-Prolyl-(L)-Proline (1) and (L)-Isoleucyl-(L)-Prolyl-(L)-Proline (2) are reported on the basis of experimental linear-polarized IR-spectroscopy in solid-state, H-1-NMR data and DFT. Curiously, the experimental data shown that both peptides stabilized in solution and in solid-state neutral H2N-RCOOH form. Conformational analysis made, shown two strong intramolecular NH2...O=C-N-(Amide) and O=C-OH...NH2 hydrogen bonds with lengths of 2.979 angstrom and 2.475 angstrom in (1) and 2.599 angstrom and 2.507 angstrom in (2) respectively. The presence of the Pro-Pro fold resulted to strong steric effect leading to the stabilization of free COOH and NH2 groups. The E-rel values of zwitterion form are significant higher than the neutral forms with a difference of 1.2 and 0.9 kJ/mol. The manner of interaction of the peptides with angiotensin-I converting enzyme is proposed.