Peptide Conformations. 42.^1,2 Conformation of Side Chains in Peptides Using Heteronuclear Coupling Constants Obtained by Two-Dimensional NMR Spectroscopy

The conformation about the C^αC^β bond of amino acid residues in peptides (xi angle) can be obtained from homo-and heteronuclear coupling constants. Ambiguities in the assignment of the most stable side-chain conformation derived from homonuclear coupling constants are resolved by the inclusion of H³C^/couplings. These coupling constants can be obtained quantitatively from various two-dimensional techniques, which, however, suffer from an inherently low signal to noise ratio. in this paper, it is shown that qualitative knowledge of heteronuclear coupling constants as obtained by the evaluation of a COLOC spectrum for the carbonyl carbons is sufficient to discriminate heteronuclear antiperiplanar coupling from synclinal coupling and thus assign the side-chain conformation unambiguously. This procedure is demonstrated on the example of amino acid residues in cyclic oligopeptides, in which the side-chain conformation was determined by other methods (such as stereoselective deuteriation or by NOE effects). ³J(H^β15N) coupling constants are shown to be useful for conformational analysis with this procedure too.