Untersuchungen über die Konformation des cyclischen Hexapeptids cyclo‐Glycyl‐L‐prolyl‐glycyl‐glycyl‐L‐prolyl‐glycyl mittels protonenmagnetischer Resonanz und Parallelen zum Cyclodecapeptid Gramicidin S. 14. Mitteilung über homodet cyclische Polypeptide [1] [2]

The first proton magnetic resonance observations made with cyclic hexapeptides suggested the presence of two types of amide protons: one participating in intramolecular hydrogen bonds and more strongly shielded, the other exposed to the solvent and less shielded (S CHWYZER , et al. 1964 [2]). This was taken as evidence for the β‐type structure proposed for homodetic cyclic peptides with 2 · (2n + 1) amino acid residues in the ring (S CHWYZER [4]), n = 1, 2, 3 … These conclusions have now been confirmed by studies on the solvent dependence of chemical shifts in cyclo ‐glycyl‐prolyl, cyclo ‐glycyl‐prolyl‐glycyl‐glycyl‐prolyl‐glycyl (III) and gramicidin S. On passing from a typical amide proton acceptor solvent (hexadeuterodimethylsulfoxide or tetradeuteromethanol) to trifluoroacetic acid the solvent‐exposed protons become more shielded and the intramolecularly hydrogen bonded ones less so (Figure 5). The proposed β‐structure of the cyclodecapeptide gramicidin S (n = 2 in the above formula; H ODGKIN & O UGHTON [8], crystalline state; S CHWYZER [9], in solution) which has recently been supported by side‐chain interaction studies (using a nuclear magnetic resonance marker) on the biologically active derivative, diphthalylgramicidin S (S CHWYZER & L UDESCHER [1]) as well as by other methods [6] [7], is thus additionally supported. Our experiments, as well as those of K OPPLE [11], strongly favor a β‐structure for simple cyclohexapeptides in solution; this is particularly true for compound III which is, with respect to the two proline residues, a model of gramicidin S.