Laboratory of Molecular Materials, Division of Biophysics and Bioengineering, Department of Physics, Chemistry and Biology, Linköping University, 581 83 Linköping, Sweden.
Laboratory of Molecular Materials, Division of Biophysics and Bioengineering, Department of Physics, Chemistry and Biology, Linköping University, 581 83 Linköping, Sweden.
Adv Drug Deliv Rev. 2021 Mar;170:26-43. doi: 10.1016/j.addr.2020.12.012. Epub 2020 Dec 27.
Coiled coils are characterized by an arrangement of two or more α-helices into a superhelix and one of few protein motifs where the sequence-to-structure relationship to a large extent have been decoded and understood. The abundance of both natural and de novo designed coil coils provides a rich molecular toolbox for self-assembly of elaborate bespoke molecular architectures, nanostructures, and materials. Leveraging on the numerous possibilities to tune both affinities and preferences for polypeptide oligomerization, coiled coils offer unique possibilities to design modular and dynamic assemblies that can respond in a predictable manner to biomolecular interactions and subtle physicochemical cues. In this review, strategies to use coiled coils in design of novel therapeutics and advanced drug delivery systems are discussed. The applications of coiled coils for generating drug carriers and vaccines, and various aspects of using coiled coils for controlling and triggering drug release, and for improving drug targeting and drug uptake are described. The plethora of innovative coiled coil-based molecular systems provide new knowledge and techniques for improving efficacy of existing drugs and can facilitate development of novel therapeutic strategies.
螺旋线圈的特征是将两个或更多的α-螺旋排列成一个超螺旋，并且是少数几个蛋白质基序之一，其中序列到结构的关系在很大程度上已经被解码和理解。天然和从头设计的螺旋线圈的丰富性为精心设计的分子结构、纳米结构和材料的自组装提供了丰富的分子工具包。利用大量的可能性来调整多肽寡聚化的亲和力和偏好，螺旋线圈提供了独特的可能性来设计模块化和动态的组装体，这些组装体可以以可预测的方式对生物分子相互作用和细微的物理化学线索做出反应。在这篇综述中，讨论了在设计新型治疗剂和先进药物输送系统中使用螺旋线圈的策略。描述了螺旋线圈在药物载体和疫苗生成中的应用，以及使用螺旋线圈控制和触发药物释放、提高药物靶向和药物摄取的各个方面。大量创新的基于螺旋线圈的分子系统为提高现有药物的疗效提供了新的知识和技术，并有助于开发新的治疗策略。
