Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK, 2100, Copenhagen Ø, Denmark.
J Pept Sci. 2013 Nov;19(11):669-75. doi: 10.1002/psc.2548. Epub 2013 Sep 9.
We present the antimicrobial and hemolytic activities of the decapeptide anoplin and 19 analogs thereof tested against methicillin-resistant Staphylococcus aureus ATCC 33591 (MRSA), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), vancomycin-resistant Enterococcus faecium (ATCC 700221) (VRE), and Candida albicans (ATCC 200955). The anoplin analogs contain substitutions in amino acid positions 2, 3, 5, 6, 8, 9, and 10. We use these peptides to study the effect of altering the charge and hydrophobicity of anoplin on activity against red blood cells and microorganisms. We find that increasing the charge and/or hydrophobicity improves antimicrobial activity and increases hemolytic activity. For each strain tested, we identify at least six anoplin analogs with an improved therapeutic index compared with anoplin, the only exception being Enterococcus faecium, against which only few compounds are more specific than anoplin. Both 2Nal(6) and Cha(6) show improved therapeutic index against all strains tested.
我们研究了十肽 anoplin 及其 19 种类似物的抗菌和溶血活性，这些类似物针对耐甲氧西林金黄色葡萄球菌 ATCC 33591（MRSA）、大肠杆菌（ATCC 25922）、铜绿假单胞菌（ATCC 27853）、万古霉素耐药粪肠球菌（ATCC 700221）（VRE）和白色念珠菌（ATCC 200955）进行了测试。anoplin 类似物在氨基酸位置 2、3、5、6、8、9 和 10 处发生取代。我们使用这些肽来研究改变 anoplin 的电荷和疏水性对其针对红细胞和微生物的活性的影响。我们发现，增加电荷和/或疏水性可以提高抗菌活性并增加溶血活性。对于每种测试的菌株，我们确定了至少六种 anoplin 类似物，与 anoplin 相比，它们的治疗指数有所提高，唯一的例外是粪肠球菌，与 anoplin 相比，只有少数化合物对其具有更高的特异性。2Nal(6)和 Cha(6)对所有测试菌株均显示出改善的治疗指数。
