目前提出的抗菌肽的作用机制模型都是基于静电引力与细胞膜上阴离子磷脂结合，并通过特有的两亲性α-helix结构插入膜磷脂双分子层形成短暂的膜孔洞或胶束而杀死细菌。尽管已经发现的抗菌肽结构各异，但认为两亲性α-helix结构是具备抗菌活性的重要结构特征。我们从两栖类皮肤分泌物中发现一类具有任意伸展结构的新型抗菌肽能以微摩尔浓度选择性杀死G+细菌。对于这类非两亲性α-helix结构的抗菌肽选择性杀死细菌的现象很显然无法用以前提出的杀菌机制来解释。本研究从螺旋度、整体疏水性和两亲性以及单个氨基酸等结构参数与抗菌活性和溶血性之间的关系研究具有任意伸展结构抗菌肽的构效关系；并从细胞膜结构和形态、细胞膜受体、细胞内细胞器以及细胞DNA复制等方面系统研究具有任意伸展结构抗菌肽杀死细菌的主要途径，作用靶点及可能的分子生物学机制，探讨经典机制以外的作用机制，为抗菌肽作为新型抗菌药物的可行性并提供理论依据。

Several different models of AMPs have been proposed to explain how, following initial attachment, antibacterial peptides insert into the bacterial membrane to form transmembrane pores which result in membrane permeabilization. Regardless of their precise mode of action, the activities of AMPs are almost universally dependent upon amphiphilic α-helical structure, as hydrophobic regions are necessary to interact directly with the lipid components of the membrane, while hydrophilic regions either interact with the phospholipid head groups or face the lumen of the pore. Generally, these models can explain the poreforming ability of α-helical AMPs; however, the mechanisms utilized by random coil peptides have not been as well studied. While some random coil AMPs can exhibit high antimicrobial activity, there is little experimental evidence to indicate which of these models is applicable to peptides with random coil conformation. Different from the known AMPs with amphiphilic α-helical structure, we obtained a novel AMPs chensinin-1 with selective bactericidal activity against Gram-positive bacteria from the skin secretions of Chinese brown frog which specially mainly adopted an random coil structure in membrane-mimetic environment. So, chensinin-1 may be a novel lead molecule for the study of AMPs with atypical structure. In order to understand better the biological activities of AMPs with random coil conformation, we are first planing to study the structure-activity relationship by the effect of helicity, hydrophobicity, amphipathicity and amino acid composition on antimicrobial and hemolytic activity. Furthermore, we are particularly interested in the bactericidal mechanism of AMPs with random coil conformation. To do that, we will systematiclly studied the bactericidal way and target of AMPs with random coil conformation by the changes in structure of cytoplasmic membrane, membrane receptor, organelle and DNA. We hope that this present study will provide an additional stimulus to consideration of these molecules as a new class of therapeutic agents.