Cathelicidins play critical roles in mammalian innate immune defense against invasive bacterial infection. In addition to their broad-spectrum bactericidal effect, cathelicidins are interesting peptide-based drug templates because they have multiple functions including anti-inflammatory, wound healing, and angiogenesis promotion. This article summarizes the aim and method of cathelicidin molecular designs. Residue mutation, fragment assembly, chemical modification, and construction of conjugates and dimers are usually used to increase the biological activities. Addition or deletion of certain residues, disruption of leucine zipper and phenylalanine zipper are used to reduce the hemolysis and cytotoxicity. By substituting L-amino acids with D-amino acids, circular constructions and immobilization, cathelicidins' in vitro and in vivo stability could be greatly enhanced, especially their proteinase resistance.
Cathelicidins 作为大多数脊椎动物所特有的宿主防御肽，除了具有高效广谱的抗菌活性外，还具有如抗炎症、伤口修复、抑制组织损伤和促进血管生成等重要活性，因此成为蛋白多肽类新药研发热点。近年来，以其为模板进行的结构改造主要有以下几类：通过点突变、氨基酸替换、活性片段拼接、化学修饰以及轭合物和二聚体构建等手段提高cathelicidins 的生物学活性；通过添加或删减氨基酸残基和破坏Leu 和Phe 拉链结构等手段可以降低cathelicidins 的细胞毒性和溶血活性；通过D-型氨基酸替换L-型氨基酸、构建环形和固位型cathelicidins 的方式增强其体内外稳定性等。.
Keywords: cathelicidins; function; molecular design; stability; structure.