The peptide α-helix is right-handed when containing amino acids with L-chirality, and left-handed with D-chirality, however mixed chirality peptides generally do not form α-helices unless a helix inducer such as the non-natural residue amino-isobutyric acid is used. Herein we report the first X-ray crystal structures of mixed chirality α-helices in short peptides comprising only natural residues as the example of a stapled bicyclic and a linear membrane disruptive amphiphilic antimicrobial peptide (AMP) containing seven L- and four D-residues, as complexes of fucosylated analogs with the bacterial lectin LecB. The mixed chirality α-helices are superimposable onto the homochiral α-helices and form under similar conditions as shown by CD spectra and MD simulations but non-hemolytic and resistant to proteolysis. The observation of a mixed chirality α-helix with only natural residues in the protein environment of LecB suggests a vast unexplored territory of α-helical mixed chirality sequences and their possible use for optimizing bioactive α-helical peptides.

中文翻译：

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X 射线晶体学揭示了双环和线性抗菌肽中的混合手性 α-螺旋

肽α螺旋是含有与氨基酸时右手大号-chirality，并用左手d -chirality，然而混合手性肽通常不形成α螺旋除非螺旋诱导剂如非天然残基的氨基酸- 使用异丁酸。在此，我们报告了仅包含天然残基的短肽中混合手性 α-螺旋的第一个 X 射线晶体结构，例如包含七个L - 和四个D 的双环和线性膜破坏性两亲抗菌肽 (AMP)-残基，作为岩藻糖基化类似物与细菌凝集素 LecB 的复合物。混合手性 α-螺旋可叠加到同手性 α-螺旋上，并在类似条件下形成，如 CD 光谱和 MD 模拟所示，但非溶血性和抗蛋白水解。在 LecB 的蛋白质环境中观察到只有天然残基的混合手性 α-螺旋表明 α-螺旋混合手性序列的广阔未开发领域及其可能用于优化生物活性 α-螺旋肽。