Guanidylation and tail effects in cationic antimicrobial lipopeptoids.
Guanidylation and tail effects in cationic antimicrobial lipopeptoids.
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DOI：
10.1371/journal.pone.0041141
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Schweizer F
中科院分区：
文献类型：
--
作者：
Findlay B;Szelemej P;Zhanel GG;Schweizer F
阳离子抗菌肽 (CAMP) 是下一代抗菌化合物的有吸引力的支架，因为它们对多重耐药细菌具有广谱活性，并且 CAMP 不敏感突变体的适应性降低。不幸的是，它们受到体内性能较差的限制，包括容易被内源血清蛋白酶裂解。为了探索类肽残基取代经过充分研究的 CAMP 支架的潜力，我们生产了一系列抗菌脂肽，其序列与之前报道的脂肽相似。针对一组临床相关和实验室参考细菌评估类肽的活性，并通过溶血测试和在添加牛血清白蛋白 (BSA) 的情况下重复抗菌测试来确定非特异性结合的可能性。最活跃的类肽对大多数测试的革兰氏阳性菌株表现出良好至中等的活性，对革兰氏阴性菌株表现出中等至有限的活性。抗菌活性与对真核细胞的毒性呈正相关，但通过添加 BSA 几乎完全消除。类脂肽与之前报道的脂肽具有相似的活性，证实了它们作为 CAMP 的替代、蛋白水解稳定支架的潜力。
Cationic antimicrobial peptides (CAMPs) are attractive scaffolds for the next generation of antimicrobial compounds, due to their broad spectrum of activity against multi-drug resistant bacteria and the reduced fitness of CAMP-insensitive mutants. Unfortunately, they are limited by poor in vivo performance, including ready cleavage by endogenous serum proteases. To explore the potential for peptoid residues to replace well studied CAMP scaffolds we have produced a series of antimicrobial lipopeptoids, with sequences similar to previously reported lipopeptides. The activity of the peptoids was assessed against a panel of clinically relevant and laboratory reference bacteria, and the potential for non-specific binding was determined through hemolytic testing and repeating the antimicrobial testing in the presence of added bovine serum albumin (BSA). The most active peptoids displayed good to moderate activity against most of the Gram positive strains tested and moderate to limited activity against the Gram negatives. Antimicrobial activity was positively correlated with toxicity towards eukaryotic cells, but was almost completely eliminated by adding BSA. The lipopeptoids had similar activities to the previously reported lipopeptides, confirming their potential to act as replacement, proteolytically stable scaffolds for CAMPs.
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影响因子：
56.9
作者：
McDaniel, Lauren D.;Young, Elizabeth;Paul, John H.
通讯作者：
Paul, John H.
DOI：
10.1073/pnas.0806456105
发表时间：
2008-12-30
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
4.9
作者：
Zhanel, George G.;DeCorby, Mel;Hoban, Daryl J.
通讯作者：
Hoban, Daryl J.
DOI：
10.1098/rspb.2005.3301
发表时间：
2006-01-22
影响因子：
4.7
作者：
Perron, GG;Zasloff, M;Bell, G
通讯作者：
Bell, G