Antimicrobial Peptides with Potential for Biofilm Eradication: Synthesis and Structure Activity Relationship Studies of Battacin Peptides

被引:110
作者
De Zoysa, Gayan Heruka [1 ]
Cameron, Alan James [1 ]
Hegde, Veena V. [2 ]
Raghothama, Srinivasarao [2 ]
Sarojini, Vijayalekshmi [1 ]
机构
[1] Univ Auckland, Sch Chem Sci, Auckland 1, New Zealand
[2] Indian Inst Sci, NMR Res Ctr, Bangalore 560012, Karnataka, India
关键词
POLYMYXIN-B NONAPEPTIDE; SYRINGAE PV. ACTINIDIAE; BACTERIAL CANKER; INNER MEMBRANE; OUTER; IMMOBILIZATION; ANTIBIOTICS; KIWIFRUIT; MAGAININ;
D O I
10.1021/jm501084q
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
We report on the first chemical syntheses and structureactivity analyses of the cyclic lipopeptide battacin which revealed that conjugation of a shorter fatty acid, 4-methyl-hexanoic acid, and linearization of the peptide sequence improves antibacterial activity and reduces hemolysis of mouse blood cells. This surprising finding of higher potency in linear lipopeptides than their cyclic counterparts is economically beneficial. This novel lipopeptide was membrane lytic and exhibited antibiofilm activity against Pseudomonas aeruginosa, Staphylococcus aureus, and, for the first time, Pseudomonas syringe pv. actinidiae. The peptide was unstructured in aqueous buffer and dimyristoylphosphatidylcholine-polymerized diacetylene vesicles, with 12% helicity induced in 50% v/v of trifluoroethanol. Our results indicate that a well-defined secondary structure is not essential for the observed antibacterial activity of this novel lipopeptide. A truncated pentapeptide conjugated to 4-methyl hexanoic acid, having similar potency against Gram negative and Gram positive pathogens was identified through alanine scanning.
引用
收藏
页码:625 / 639
页数:15
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