Stable Right- and Left-Handed Peptide Helices containing Cα-Tetrasubstituted α-Amino Acids

Short peptidomimetics with stable secondary structures in solution are of interest for applications in chemistry, biology, and medicine. One way to rigidify the backbone of a peptide is the use of cyclic Cα-tetrasubstituted α-amino acids (TAAs) like compound 14. The structures resulting from the incorporation of this unnatural amino acid into peptides were investigated. In total, 13 different peptides with a length of up to eight residues and alternating sequences of TAA 14 and (S)- or (R)-valine were synthesized. Their structures were characterized by X-ray diffraction analysis and NMR and CD measurements showing that the all-S-backbone-configured peptides 5 and 6 (SS)2−3 form right-handed 310-helices, while the all-R-configured peptides 11−13 (RR)2−4 form left-handed 310-helices in the solid state and solution.

在溶液中具有稳定二级结构的短肽模拟物对于化学、生物学和医学领域的应用具有重要意义。通过使用如化合物14这样的环状Cα四取代α-氨基酸（TAAs）来刚化肽的骨架是一种常见的方法。将这种非天然氨基酸引入肽中产生的结构已得到研究。总计合成了13种长度不超过八个残基、交替序列为TAA 14以及（S）-或（R）-缬氨酸的肽。通过X射线衍射分析、核磁共振和圆二色光谱测量对其结构进行了表征，结果显示所有-S骨架配置的肽5和6（SS）2−3形成右手310螺旋，而所有-R配置的肽11−13（RR）2−4在固态和溶液中形成左手310螺旋。