两亲α-螺旋抗菌肽的分子设计研究现状与进展

抗菌肽以其广谱、快速、特异性作用及抗菌、抗病毒、抗肿瘤等活性,成为具有重要潜在价值的新型药物.最大限度地发挥其活性和降低毒性,是抗菌肽新药开发的首要问题.用分子设计手段改造抗菌肽已成为解决这一问题的关键.以两亲α-螺旋抗菌肽为对象,对分子设计过程中遵守阳离子性和两亲性的原则及影响活性的物理化学参数,可以采取序列修饰或全新设计的方法,以达到定向改造的目的.对分子设计在医药上的应用和发展前景进行了综述和展望.

Current status and trends in molecular design of antimicrobial peptides: amphipathic-helix motif

Antimicrobial peptides, termed bacteriocins, are being increasingly recognized as potential candidate therapeutic drugs with reference to their broad-spectrum, rapid and specific activities against virus, bacteria and tumor cells. However, a precise understanding of the relationship between antimicrobial peptide structure and their cytolytic functions in a range of organisms is still lacking. A major target of molecular biotechnique is the design of new potent antimicrobial peptides which have optimal, lytic activity against pathogen and less toxicity, e.g., haemolytic activity, to host. This review details the current status and trends in the study of molecular design with respect to amphipathic-helical antimicrobial peptides. The relationship of the cationic-amphipathic antimicrobial peptides rule to the related physicochemical parameters, including size, charge and amphipathicity, were discussed. Several methods used in both the sequence modification and the de,nove design were introduced.