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[摘要]：The conformational properties of foldamers generated from ag hybrid peptide sequences have been probed in the model sequence and gabapentin (Gpn) residues greatly restricts sterically accessible conformational space. This model sequence was anticipated to be a short segment of the ag C12 helix, stabilized by three successive 4? hydrogen bonds, corresponding to a backbone-expanded analog of the a polypeptide 310-helix. Unexpectedly, three distinct cryst. polymorphs were characterized in the solid state by X-ray diffraction. In one form, two successive C12 hydrogen bonds were obtained at the N-terminus, while a novel C17 hydrogen-bonded gag turn was obsd. at the C-terminus. In the other two polymorphs, isolated C9 and C7 hydrogen-bonded turns were obsd. at Gpn (2) and Gpn (4). Isolated C12 and C9 turns were also crystallog. established in the peptides Boc-Aib-Gpn-Aib-OMe and Boc-Gpn-Aib-NHMe, resp. Selective line broadening of NH resonances and the observation of medium range NH(i) U NH(i+2) NOEs established the presence of conformational heterogeneity for the tetrapeptide in CDCl3 soln. The NMR results are consistent with the limited population of the continuous C12 helix conformation. Lengthening of the (ag)n sequences in the nonapeptides Boc-Aib-Gpn-Aib-Gpn-Aib-Gpn-Aib-Gpn-Xxx (Xxx = Aib, Leu) resulted in the observation of all of the sequential NOEs characteristic of an ag C12 helix. These results establish that conformational fragility is manifested in short hybrid ag sequences despite the choice of conformationally constrained residues, while stable helixes are formed on chain extension. |
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