15N‐NMR spectroscopy. III. Neighboring residue effects in sequence polymers containing glycylglycine units

The tripeptides Phe-Gly-Gly, β-Ala-Gly-Gly, and ϵ-Aca-Gly-Gly as well as the peptide derivatives δ-isothiocyanatovaleroyl-Gly-Gly and ϵ-isothiocyanatocaproyl-Gly-Gly were synthesized by using known methods so that the peptide nitrogen between the two glycyl residues was isotopically enriched in 15N to a level of 0.8–0.9%. These monomer units were then used to produce the sequence polymers (Phe-Gly-Gly)n, (β-Ala-Gly-Gly)n, (δ-Ava-Gly-Gly)n, and (ϵ-Aca-Gly-Gly)n. The 18.24 MHz 15N-NMR spectra of the oligo- and polypeptides were obtained by using trifluoroacetic acid as solvent, since the solutions have relatively low viscosity and exhibit a strong negative nuclear Overhauser enhancement of the 15N signals. For comparison, 15N-NMR spectra of the homopolymers (Gly)n, (β-Ala)n, (γ-Abu)n, (δ-Ava)n, and (ϵ-Aca)n were also recorded. The 15N signals from the ω-aminoacyl residues in the sequence polymers appear up to 11 ppm upfield of the signals observed for the homopolyamides. The 15N signals from the two glycyl residues are separated by 3–7 ppm. Comparison with the 13C-NMR spectra of the same polymers indicates that 15N-NMR is better suited for the characterization and sequence analysis of these types of polymers.