Zhang Qi, Li Xiaojing, Huang Kui, Huang Yongjie, Zhao Suwen, Liu Shanshan, Li Yang
Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
Surgical Intensive Care Unit of Department of Critical Care Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
Biomacromolecules. 2023 Apr 10;24(4):1689-1699. doi: 10.1021/acs.biomac.2c01475. Epub 2023 Mar 27.
Collagen hybridizing peptides (CHPs) are a powerful tool for targeting collagen damage in pathological tissues due to their ability to specifically form a hybrid collagen triple-helix with the denatured collagen chains. However, CHPs have a strong tendency to self-trimerize, requiring preheating or complicated chemical modifications to dissociate their homotrimers into monomers, which hinders their applications. To control the self-assembly of CHP monomers, we evaluated the effects of 22 cosolvents on the triple-helix structure: unlike typical globular proteins, the CHP homotrimers (as well as the hybrid CHP-collagen triple helix) cannot be destabilized by the hydrophobic alcohols and detergents (e.g., SDS) but can be effectively dissociated by the cosolvents that dominate hydrogen bonds (e.g., urea, guanidinium salts, and hexafluoroisopropanol). Our study provided a reference for the solvent effects on natural collagen and a simple effective solvent-switch method, enabling CHP utilization in automated histopathology staining and in vivo imaging and targeting of collagen damage.
胶原杂交肽（CHPs）是一种用于靶向病理性组织中胶原损伤的强大工具，因为它们能够与变性的胶原链特异性形成杂交胶原三螺旋。然而，CHPs具有强烈的自我三聚化倾向，需要预热或复杂的化学修饰才能将其同三聚体解离成单体，这阻碍了它们的应用。为了控制CHP单体的自组装，我们评估了22种共溶剂对三螺旋结构的影响：与典型的球状蛋白质不同，CHP同三聚体（以及杂交CHP-胶原三螺旋）不会被疏水醇和去污剂（如SDS）破坏稳定性，但可以被主导氢键的共溶剂（如尿素、胍盐和六氟异丙醇）有效解离。我们的研究为溶剂对天然胶原的影响提供了参考，并提供了一种简单有效的溶剂转换方法，使CHP能够用于自动组织病理学染色以及体内成像和胶原损伤靶向。
