Tsunekawa Eisuke, Nakama Takahiro, Fujita Makoto, Sawada Tomohisa
Department of Applied Chemistry, School of Engineering, The University of Tokyo, Mitsui Link Lab Kashiwanoha 1, FS CREATION 6-6-2 Kashiwanoha Kashiwa Chiba 277-0882 Japan.
Division of Advanced Molecular Science, Institute for Molecular Science, National Institutes of Natural Sciences 5-1 Higashiyama, Myodaiji-cho Okazaki Aichi 444-8787 Japan.
Chem Sci. 2025 Sep 9. doi: 10.1039/d5sc05237h.
Natural and artificial β-sheet assemblies often form helical structures due to the inherent twisting of peptide strands, typically observable by AFM and TEM but rarely analysed with single crystal X-ray diffraction (SCD) due to structural disorder. This study overcame such challenges by periodically cross-linking peptide strands in β-sheet tapes metal coordination, creating perfectly ordered helical structures suitable for SCD analysis. Side chain interactions were found to drive helical twisting, and adjusting side chain substituents enabled tuning of the helical morphology, including the formation of double helices. These findings open new possibilities in β-sheet assembly design, advancing peptide engineering.
天然和人工的β-折叠组装体常常由于肽链固有的扭曲而形成螺旋结构，通常可通过原子力显微镜（AFM）和透射电子显微镜（TEM）观察到，但由于结构无序，很少用单晶X射线衍射（SCD）进行分析。本研究通过金属配位使β-折叠带中的肽链周期性交联，克服了这些挑战，创造出了适合SCD分析的完美有序螺旋结构。研究发现侧链相互作用驱动螺旋扭曲，调整侧链取代基能够调节螺旋形态，包括双螺旋的形成。这些发现为β-折叠组装体设计开辟了新的可能性，推动了肽工程的发展。
