Dennison Sarah R, Morton Leslie H G, Harris Frederick, Phoenix David A
School of Pharmacy and Biomedical Sciences, University of Central Lancashire Preston, Preston, PR1 2HE, UK.
Eur Biophys J. 2014 Jul;43(6-7):255-64. doi: 10.1007/s00249-014-0959-8. Epub 2014 Apr 13.
Aurein 2.5 (GLFDIVKKVVGAFGSL-NH2) is an antimicrobial peptide, which was seen to have activity against Stachybotris chartarum, Penicillium roseopurpureum and Aspergillus flavus with minimum fungicidal concentrations in the range 250-500 μM. S. chartarum showed enhanced susceptibility to lysis as compared to P. roseopurpureum and A. flavus, (44, 26 and 28 % respectively). Monolayers formed from lipid membrane extracts derived from S. chartarum, P. roseopurpureum and A. flavus showed maximal surface pressure changes of 13.5, 10.3 and 10.2 mN m(-1) respectively. However, aurein 2.5 adopted similar levels of α-helical structure (circa 45 %) in the presence of vesicles formed from membrane lipid extracts derived from all three fungi. These data imply that differential activity is not due to targeting and membrane association but linked to the ability of the bound peptide to lyse the cells. At sterol levels mimetic of eukaryotic systems, high levels of α-helical structure (circa 50 %) were also observed and hence similar binding. However, enhanced sterol levels (>0.6) led to a reduction in monolayer membrane interaction, suggesting that the sterols influence efficacy. Consistent with this suggestion, thermodynamic analysis showed that the peptide was able to destabilise model fungal monolayers, as indicated by negative values of ∆Gmix.
奥瑞因2.5（GLFDIVKKVVGAFGSL-NH2）是一种抗菌肽，已发现其对炭疽杆菌、玫瑰紫青霉和黄曲霉具有活性，最低杀菌浓度在250 - 500μM范围内。与玫瑰紫青霉和黄曲霉相比，炭疽杆菌对裂解表现出更高的敏感性（分别为44%、26%和28%）。由炭疽杆菌、玫瑰紫青霉和黄曲霉的脂质膜提取物形成的单层膜分别显示出最大表面压力变化为13.5、10.3和10.2 mN m(-1)。然而，在由所有三种真菌的膜脂质提取物形成的囊泡存在的情况下，奥瑞因2.5呈现出相似水平的α-螺旋结构（约45%）。这些数据表明，差异活性并非由于靶向作用和与膜的结合，而是与结合的肽裂解细胞的能力有关。在模拟真核系统的甾醇水平下，也观察到了高水平的α-螺旋结构（约50%），因此结合情况相似。然而，甾醇水平升高（>0.6）导致单层膜相互作用减少，表明甾醇会影响功效。与这一推测一致，热力学分析表明，该肽能够使模型真菌单层膜不稳定，∆Gmix值为负即表明了这一点。
