铰链结构对抗菌肽生物活性的影响及在分子设计中的应用研究进展

The effects of hinge structure on the biological activity of antimicrobial peptides and its application in molecular design: a review

摘要:

铰链结构，又称铰链区或转角，是部分抗菌肽序列中存在的一种特殊结构。但目前抗菌肽结构的研究多集中于标准的α-螺旋和β-折叠二级结构，对于铰链结构及其作用总结较少。铰链结构对抗菌肽生物活性有重要影响，主要原因是铰链结构能够提高抗菌肽的结构灵活性，促进其对细菌细胞膜的破坏作用或与胞内作用靶点的结合效率，进而提高抗菌肽的抗菌活性。同时，降低的抗菌肽结构刚性，消减了抗菌肽对真核细胞的毒性。文中结合了笔者课题组相关工作，就铰链结构特点、对抗菌肽生物活性的影响以及在抗菌肽分子设计方面的应用进行了综述，以期为新型抗菌肽的设计和开发提供参考。

Abstract:

The hinge structure, also known as hinge region or bend, is a special structure found in some antimicrobial peptides. Most studies on antimicrobial peptides focused on the standard secondary structure of α-helix and β-sheet, while the hinge structure and its functions were rarely studied. The hinge structure confers the antimicrobial peptides an improved structural flexibility, which may promote their disruptive effect on bacterial membrane or their binding efficiency to the intracellular targets, thus resulting in a higher antibacterial activity. Meanwhile, the hinge structure may reduce the structural rigidity, which may eliminate the cytotoxicity of antimicrobial peptides to eukaryotic cells. This article reviews the structural characteristics of the hinge structure, its effects on the biological activity of antimicrobial peptides and application in the molecular design, with the aim to provide a reference for the design and development of new antimicrobial peptides.