Muñoz Alberto, López-García Belén, Pérez-Payá Enrique, Marcos Jose F
Instituto de Agroquímica y Tecnología de Alimentos (IATA)-CSIC, Apartado de Correos 73, Burjassot, 46100 Valencia, Spain.
Biochem Biophys Res Commun. 2007 Mar 2;354(1):172-7. doi: 10.1016/j.bbrc.2006.12.173. Epub 2007 Jan 12.
Short antimicrobial peptides represent an alternative to fight pathogen infections. PAF26 is a hexapeptide identified previously by a combinatorial approach against the fungus Penicillium digitatum and shows antimicrobial properties towards certain phytopathogenic fungi. In this work, PAF26 was used as lead compound and its properties were compared with two series of derivatives, obtained by either systematic alanine substitution or N-terminal amino acid addition. The alanine scan approach underlined the optimized sequence of PAF26 in terms of potency and permeation capability, and also the higher contribution of the cationic residues to these properties. The N-terminal addition of amino acids resulted in new heptapeptides with variations in their antimicrobial characteristics, and very low cytolysis to human red blood cells. Positive (Arg or Lys) and aromatic (Phe or Trp) residue addition increased broad spectrum activity of PAF26. Noteworthy, addition of selected residues had specific effects on the properties of derivatives of PAF26.
短抗菌肽是对抗病原体感染的一种替代方法。PAF26是先前通过针对指状青霉的组合方法鉴定出的一种六肽，对某些植物致病真菌具有抗菌特性。在这项工作中，PAF26被用作先导化合物，并将其性质与通过系统丙氨酸取代或N端氨基酸添加获得的两个系列衍生物进行了比较。丙氨酸扫描方法强调了PAF26在效力和渗透能力方面的优化序列，以及阳离子残基对这些性质的更大贡献。N端添加氨基酸产生了具有不同抗菌特性且对人红细胞细胞溶解作用极低的新七肽。添加正电荷（精氨酸或赖氨酸）和芳香族（苯丙氨酸或色氨酸）残基增加了PAF26的广谱活性。值得注意的是，添加特定残基对PAF26衍生物的性质有特定影响。
