Departamento de Química Orgánica, Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Universidade de Santiago de Compostela, 15705, Santiago de Compostela, Spain.
Nat Commun. 2024 Aug 14;15(1):6987. doi: 10.1038/s41467-024-51072-8.
The structure of helical polymers is dictated by the molecular chirality of their monomer units. Particularly, macromolecular helices with monomer sequence control have the potential to generate chiral topologies. In α-helical folded peptides, the sequential repetition of amino acids generates a chiral layer defined by the amino acid side chains projected outside the amide backbone. Despite being closely related to peptides' structural and functional properties, to the best of our knowledge, a general exo-helical symmetry model has not been yet described for the α-helix. Here, we perform the theoretical, computational, and spectroscopic elucidation of the α-helix principal exo-helical topologies. Non-canonical labeled amino acids are employed to spectroscopically characterize the different exo-helical topologies in solution, which precisely match the theorical prediction. Backbone-to-chromophore distance also shows the expected impact in the exo-helices' geometry and spectroscopic fingerprint. Theoretical prediction and spectroscopic validation of this exo-helical topological model provides robust experimental evidence of the chiral potential on the surface of helical peptides and outlines an entirely new structural scenario for the α-helix.
螺旋聚合物的结构由其单体单元的分子手性决定。特别是具有单体序列控制的高分子螺旋体有可能产生手性拓扑结构。在α-螺旋折叠肽中，氨基酸的顺序重复生成了一个由氨基酸侧链在外肽骨架外突出定义的手性层。尽管与肽的结构和功能特性密切相关，但据我们所知，尚未为α-螺旋描述一般的外螺旋对称模型。在这里，我们对α-螺旋的主要外螺旋拓扑结构进行了理论、计算和光谱阐明。使用非规范标记的氨基酸在溶液中对不同的外螺旋结构进行光谱表征，这与理论预测完全吻合。骨干到生色团的距离也显示出外螺旋几何形状和光谱指纹中的预期影响。这种外螺旋拓扑模型的理论预测和光谱验证为螺旋肽表面的手性潜力提供了可靠的实验证据，并为α-螺旋勾勒出了一个全新的结构场景。
