Configurational Assignment of D‐ and L‐Isovalines in Intact, Natural, and Synthetic Peptides by 2D‐NMR Spectroscopy

This is the authors' abstract. We don't add key points for this paper.

We investigated, by means of 2D-NMR, the naturally occurring and chemically synthesized 16-mer integramides A and B, which belong to a group of bioactive, fungal peptides (peptaibiotics), that are characterized by an abundance of Aib as well as D- and L-Iva residues. The chemical shifts of the C(alpha)-alkyl groups in the Iva enantiomers depend on the alpha-C-atom configuration and on the helical screw sense of the peptides, the latter determined by CD. In the full-length, right-handed helical integramides, as well as in the partial sequences exploited for their total chemical syntheses, the gamma-Me H-atoms of the Et side chain of the D-Iva residues located near the C-terminus are significantly more shielded (delta<0.90 ppm) than those of the L-Iva residues (delta>0.95 ppm). The opposite behavior is observed for the left-handed, synthetic, intermediate Z-Aib-L-Hyp-L-Iva(14)-D-Iva(15)-O(t)Bu. Here, the gamma-Me H-atoms of L-Iva(14) are more shielded (0.838 ppm) than those of D-Iva(15) (0.905 ppm). The chemical-shift difference between the diastereotopic beta-CH(2) H-atoms of the Iva side chains in the right-handed helical peptides is much larger for D-Iva than for L-Iva. For D-Iva(14/15), the values range from 0.38 to 0.63 ppm, whereas, for D-Iva(1), the value is in the range of 0.26-0.31 ppm. In each case, the difference is always larger for the d-Iva than for the l-Iva residues (which is always <or=0.19 ppm). Again, an opposite behavior is seen for the left-handed tetrapeptide. Overall, our method enables the nondestructive assignment of the configuration of each Iva residue in peptides of known helical screw sense.