Peptide Conformations. 15. One- and Two-Dimensional ¹H, ¹³C, and ¹⁵N NMR Studies of cyclo(Pro-Phe-Gly-Phe-Gly)_n (n = 1, 2): Selective Complexation of Lithium Ions (n = 1) and Potassium Ions (n = 2)

The cyclic pentapeptide cyclco(Pro-Phe-Gly-Phe-Gly) (1), the cyclic decapeptide with dimer sequence 2, and four specifically deuterated derivatives were synthesized and studied by NMR spectroscopy. Two-dimensional correlation techniques, such as SECSY spectroscopy to determine proton connectivities, and ¹H⁻¹³C as well as ¹H⁻¹⁵N shift correlation were applied. Carbon chemical shifts and 1J_NH coupling constants measured by the INEPT technique prove the all-trans conformation of the amide bonds. A conformation containing two intramolecular hydrogen bonds (βI about the amino acids Gly⁵-Pro¹-Phe²-Gly³ and γⁱ about Gly³-Phe⁴-Gly⁵) was derived for 1, whereas a conformation with four internally oriented hydrogen bonds similar to a β-pleated sheet fits best the experimental data for 2. Complexation of lithium and sodium ions by 1 yields drastic changes in CD and ¹H NMR spectra. The conformation of the peptide within the lithium complex was derived from the ¹H NMR data. Contrary to the preferred binding of Li⁺ by 1, only potassium forms a weak complex with the cyclic decapeptide 2.