Collagen-based structures containing the peptoid residue N-isobutylglycine (Nleu): Conformational analysis of Gly-Nleu-Pro sequences by H-1-NMR and molecular modeling

Molecular modeling and H-1-NMR were employed to study the structure and stability of collagenlike triple helices composed of Gly-Nleu-Pro repeats. The compounds studied include the acetyl analogs Ac-(Gly-Nleu-Pro)(n)-NH2 (where n = 1, 3, 6, and 10) and the KTA conjugates KTA-[Gly-(Gly-Nleu-Pro)(n)-NH2](3) (where n = 3 and 6 and KTA denotes the Kemp triacid). The presence of collagen-like assembled structures is supported by a consistent set of experimental observations, which include the appearance of a distinct set of resonances, low hydrogen-exchange rates for Gly NH, cooperative melting transition, and observation of several interchain NOEs. Using H-1-NMR, the triple helicity was monitored as a function of chain length, template, and temperature. These studies show that (Gly-Nleu-Pro)(n) sequences have a somewhat higher triple-helical propensity than (Gly-Pro-Nleu)(n) sequences. In addition, our investigations have shown that unlike the triple helices composed of Gly-Pro-Nleu repeats those composed of Gly-Nleu-Pro repeats can access conformations in which the Nleu side chains are arrayed between Pro residues belonging to different triple-helix cross sections. These structural features may serve as a basis for free energy computations and for the study of higher-order structures such as collagen-like fibrils containing peptoid moities.