Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
Bioorg Med Chem Lett. 2013 Jul 1;23(13):3749-52. doi: 10.1016/j.bmcl.2013.05.002. Epub 2013 May 9.
The lipophilic amino acid, (S)-2-aminoundecanoic acid, was synthesized and incorporated at a number of specific positions within the peptide sequence of anoplin. These lipophilic anoplin analogs showed to be more active against Escherichia coli and Staphylococcus aureus compared to native anoplin, while the EC50-value of hemolysis was at least one order of magnitude lower than the MIC values. This was in sharp contrast to the N-acylated anoplin derivative, where a gain in activity also led to a complete loss of selectivity. Thus, the incorporation of a lipophilic amino acid residue into anoplin enhanced the antimicrobial activity, while selectivity towards microbial membranes was retained.
疏水性氨基酸（S）-2-氨基十一酸被合成并掺入到 anoplin 肽序列的多个特定位置。与天然 anoplin 相比，这些疏水性 anoplin 类似物对大肠杆菌和金黄色葡萄球菌表现出更强的活性，而溶血的 EC50 值至少比 MIC 值低一个数量级。这与 N-酰化 anoplin 衍生物形成鲜明对比，其中活性的提高也导致了选择性的完全丧失。因此，将疏水性氨基酸残基掺入 anoplin 中增强了抗菌活性，同时保留了对微生物膜的选择性。
