抗菌肽广泛存在于各种生物体内，是宿主先天免疫防御系统的重要组成部分，具有抗菌谱广、不易产生耐药性等优点，有望成为治疗耐药性病原菌感染所引发疾病的理想药物。在抑杀革兰氏阴性菌过程中，抗菌肽与脂多糖的相互作用对其发挥抑菌活性至关重要，但其具体作用细节及与抑菌活性之间的内在联系仍不清楚。申请人发现抗菌肽HAL-2在抑杀大肠杆菌过程中，脂多糖可诱导其形成淀粉样纤维结构，此淀粉体结构的形成对其抑菌活性至关重要。但这种淀粉体结构形成的具体分子机制及其与HAL-2抑菌活性之间的内在联系还需深入研究。本项目拟运用核磁共振、表面等离子共振等方法，主要研究氨基酸序列长度与组成、分子构象及溶液酸碱性、离子强度、二价阳离子等对HAL-2/LPS作用体系的影响；结合体外抑菌实验，揭示HAL-2淀粉体结构发挥抑菌活性的分子机制，为阐明HAL-2作用机制提供重要理论依据，为发展有针对性的新型抗菌肽类药物奠定基础。

Antimicrobial peptides (AMPs) are important components of the innate immune systems in all living organisms. AMPs possess unusually efficient antimicrobial effects with little drug-resistant against a broad range of microorganisms, which makes them attractive candidates for the development of therapeutic drugs in the fight against resistant pathogens. The interaction between AMPs and lipopolysaccharide (LPS) contributes to its antimicrobial activity against Gram-negative bacteria. However, the molecular mechanism of interaction between them and how it relates to the activity are not clear. Our present study showed that LPS is capable of inducing HAL-2 amyloid formation when against E. coli, which may play a vital role in its antimicrobial activity. But as yet unknown molecular basis regulate that specific amyloid aggregation and the antibacterial activity. Effect factors of HAL-2/LPS system including HAL-2 size, sequence changes, conformation, pH, ionic strength and divalent cations are investigated, by using various biophysical methods, such as nuclear magnetic resonance and surface plasmon resonance. Furthermore, the interaction between amyloid formation of HAL-2 and its activity will be discovered. In conclusion, this study will increase our understanding of the molecular basis of HAL-2 mediated by LPS, and it could provide information to design novel antimicrobial peptides for future therapeutic purposes.