TRIPODAL TRISPEPTIDE SELECTOR AS A MODEL FOR ESTABLISHING THE IMPORTANCE OF HYDROGEN-BONDING IN ENANTIOMER-SEPARATION

The manner of hydrogen-bonding to peptide selectors in enantiomer sepa ration is examined with the help of a structural model. Tl-lis model r elies on a C-3-symmetric trispeptide selector, which is stabilized by a network of distinct intramolecular hydrogen bonds. A combination of experimental and theoretical tools enables us to identify the lowest-e nergy conformation of the trispeptide selector and the sites of select or-substrate interactions. Experimental tools include temperature depe ndent H-1-NMR studies, 1D-NOE-measurements, and titration experiments, .with the theoretical tools being EFF and CFF91 molecular mechanics ca lculations. The structural information deduced from these investigatio ns is shown to bear on the enantioseparation of the corresponding chir al stationary phase towards derivatized amino acids. These observation s, taken together, help to rationalize the mode of enantiomer-separati on by amide phases as involving predominantly C-7-hydrogen bonding sit es. (C) 1998 Wiley-Liss, Inc.