构建肽以模拟异质蛋白如I型胶原在破译其功能和发病机理中起关键作用。然而,由于缺乏产生具有所需功能序列且没有同三聚体作用的稳定异源三聚体的能力,该领域的进展受到严重阻碍。我们在此开发了一组三嵌段肽,其可以组装成具有所需氨基酸的胶原模拟异源三聚体,并且不受同源三聚体的干扰。三嵌段肽包含一个中央胶原样阻断和两个带相反电荷的N/C末端阻断,显示同质三聚体形成的固有无能。具有互补末端带电序列的两个配对三嵌段肽之间的有利静电吸引迅速导致具有受控链组成的稳定异源三聚体。胶原蛋白样区块与两个末端区块的独立性赋予该系统在保持异源三聚体结构的同时掺入所需氨基酸序列的适应性。三嵌段肽提供了一种通用且强大的工具来模拟异源三聚体胶原蛋白的组成和功能,并且在模拟异质蛋白质的创新肽的设计中可能具有巨大潜力。
The construction of peptides to mimic heterogeneous proteins such as type I collagen plays a pivotal role in deciphering their function and pathogenesis. However, progress in the field has been severely hampered by the lack of capability to create stable heterotrimers with desired functional sequences and without the effect of homotrimers. We have herein developed a set of triblock peptides that can assemble into collagen mimetic heterotrimers with desired amino acids and are free from the interference of homotrimers. The triblock peptides comprise a central collagen-like block and two oppositely charged N-/C-terminal blocks, which display inherent incompetency of homotrimer formation. The favorable electrostatic attraction between two paired triblock peptides with complementary terminal charged sequences promptly leads to stable heterotrimers with controlled chain composition. The independence of the collagen-like block from the two terminal blocks endows this system with the adaptability to incorporate desired amino acid sequences while maintaining the heterotrimer structure. The triblock peptides provide a versatile and robust tool to mimic the composition and function of heterotrimer collagen and may have great potential in the design of innovative peptides mimicking heterogeneous proteins.