Crystallographic Characterization of the α/β-Peptide 14/15-Helix

We report the first high-resolution structural data for the 14/15-helix, a secondary structure that is formed by oligomers with a 1:1 alternation of α- and β-amino acid residues. Previously, we concluded from NMR data that short α/β-peptides containing cyclopentane-constrained β-residues display rapid interconversion between two helical folding patterns, the 11-helix (i,i+3 CO···H−N H-bonds) and the 14/15-helix (i,i+4 CO···H−N H-bonds). Subsequent work in other laboratories, however, has called this hypothesis into question. Partial support for our original hypothesis was obtained when we obtained the first crystal structure in this α/β-peptide series, which revealed an 11-helical conformation. The present report of a 14/15-helical conformation strengthens the original hypothesis.

本研究首次报道了14/15螺旋（14/15-helix）的高分辨率结构数据，该二级结构由α-与β-氨基酸残基以1:1交替排布的寡聚体形成。此前，我们基于核磁共振（NMR）数据得出结论：带有环戊烷约束型β残基的短链α/β肽段，会在两种螺旋折叠模式间快速互变，分别为11螺旋（11-helix，i,i+3位C=O···H−N氢键）与14/15螺旋（14/15-helix，i,i+4位C=O···H−N氢键）。然而，后续其他实验室的研究对该假说提出了质疑。当我们获得该α/β肽研究体系中的首个晶体结构时，得到了对我们原始假说的部分支持——该结构呈现为11螺旋构象。本次报道的14/15螺旋构象，则进一步佐证了我们的原始假说。