Uggerhøj Lars Erik, Poulsen Tanja Juul, Munk Jens Kristian, Fredborg Marlene, Sondergaard Teis Esben, Frimodt-Moller Niels, Hansen Paul Robert, Wimmer Reinhard
Department of Chemistry and Bioscience, Aalborg University, Frederik Bajers vej 7H, 9220 Aalborg Ø (Denmark).
Chembiochem. 2015 Jan 19;16(2):242-53. doi: 10.1002/cbic.201402581. Epub 2014 Dec 21.
Antimicrobial peptides (AMPs) are promising candidates for battling multiresistant bacteria. Despite extensive research, structure-activity relationships of AMPs are not fully understood, and there is a lack of structural data relating to AMPs in lipids. Here we present the NMR structure of anoplin (GLLKRIKTLL-NH2 ) in a micellar environment. A vast library of substitutions was designed and tested for antimicrobial and hemolytic activity, as well as for changes in structure and lipid interactions. This showed that improvement of antimicrobial activity without concomitant introduction of strong hemolytic activity can be achieved through subtle increases in the hydrophobicity of the hydrophobic face or through subtle increases in the polarity of the hydrophilic face of the helix, or-most efficiently-a combination of both. A set of guidelines based on the results is given, for assistance in how to modify cationic α-helical AMPs in order to control activity and selectivity. The guidelines are finally tested on a different peptide.
抗菌肽（AMPs）是对抗多重耐药细菌的有前途的候选物。尽管进行了广泛的研究，但AMPs的构效关系尚未完全理解，并且缺乏与脂质中AMPs相关的结构数据。在这里，我们展示了在胶束环境中anoplin（GLLKRIKTLL-NH2）的核磁共振结构。设计并测试了大量的取代文库，以检测其抗菌和溶血活性，以及结构和脂质相互作用的变化。结果表明，通过微妙地增加疏水表面的疏水性或通过微妙地增加螺旋亲水性表面的极性，或者最有效的是两者结合，可以在不伴随引入强溶血活性的情况下提高抗菌活性。基于这些结果给出了一组指导原则，以协助如何修饰阳离子α-螺旋抗菌肽以控制活性和选择性。最后在一种不同的肽上测试了这些指导原则。
