Studies On The Proton Transfer Mechanisms And Relevant Properties Of Glycinamide And Its Derivatives Associated With The Cis Peptide Bond Units

More and more proteins containing cis peptide bonds have been found with the increasing resolution of X-ray and NMR experiments. Being an abnormal occurrence of peptide bonds, the cis peptide bonds are always associated with the certain structures and functional performances. However, the structural forms and stabilities of them have not yet been clarified systematically to date. In addition, there has still been a hot debate on the existence and significance of low-barrier H-bond (LBHB) in catalytic triad of serine proteases. Thus, in the present doctoral dissertation, relevant studies on the model compound glycinamide possessing the cis peptide bond unit and the existence and significance of the LBHB in the catalytic triad of serine proteases have been systematically and extensively investigated employing the Density Functional Theory (DFT). As a result, some significant progresses have been made, which can be described as follows.(1) Firstly, to pave the way for the future study, we have investigated the conformational behaviors of glycinamide in the gas phase and in solution systematically. A total of seven conformers have been located on the potential energy surface (PES) of glycinamide in the gas phase, corresponding to three pairs of mirror-image conformers and one conformer possessing the Cs symmetry. Analyses of relative energies and comparisons with relevant experimental results suggest that the global minimum of glycinamide should be characterized by the intramolecular H-bond formed between amide and amino group, which can be further confirmed by the interatomic distances, charge distributions, and vibrational analyses. Furthermore, relevant spectroscopic properties, such as IR, Raman, NMR, and VCD spectra, have been discussed to provide some helpful information for the identification of the available conformers in the gas phase. In solution, the relative stabilities among the available conformers remain the same as those of the gas phase except for the reverse order between two minor conformers due to their larger differences in dipole moments. Some significant structural changes in dihedral angles have been observed for the second minimum upon solvation. Additionally, all the IR intensities are much stronger than those in the gas phase and the characteristic bands of carbonyl group have been red-shifted.