Exploring the role of unnatural amino acids in antimicrobial peptides.
Exploring the role of unnatural amino acids in antimicrobial peptides.
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DOI：
10.1038/s41598-018-27231-5
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发表时间：
2018-06-11
影响因子：
4.6
通讯作者：
Petraccone L
中科院分区：
文献类型：
--
作者：
Oliva R;Chino M;Pane K;Pistorio V;De Santis A;Pizzo E;D'Errico G;Pavone V;Lombardi A;Del Vecchio P;Notomista E;Nastri F;Petraccone L
阳离子抗菌肽(CAMP)是治疗耐多药细菌的一种很有前途的选择，这些细菌对所有常用的抗菌素都产生了耐药性，因此对人类健康构成了严重威胁。Camp的主要缺点之一是对蛋白酶的敏感性，这极大地限制了它们的半衰期。我们设计并合成了三个具有较高血清稳定性和广谱抗菌活性的九残基环类化合物。由于所有的多肽在细菌和真核细胞之间的选择性都很低，我们对其中一种多肽与模拟细菌和真核细胞膜的脂质体的相互作用进行了详细的生物物理表征。我们的结果表明，DPPC/DPPG囊泡表面结合，再加上脂质结构域的形成，并且在阈值浓度以上，深度插入到双层疏水核心中。反之，该多肽主要结合在DPPC双层表面。这些观察到的多肽与两种模型膜相互作用的差异表明，导致抗菌活性和对哺乳动物细胞株的高毒性的机制存在差异。这些结果可能是对解开合成营地发展中一些悬而未决的问题的重要贡献。
Cationic antimicrobial peptides (CAMPs) are a promising alternative to treat multidrug-resistant bacteria, which have developed resistance to all the commonly used antimicrobial, and therefore represent a serious threat to human health. One of the major drawbacks of CAMPs is their sensitivity to proteases, which drastically limits their half-life. Here we describe the design and synthesis of three nine-residue CAMPs, which showed high stability in serum and broad spectrum antimicrobial activity. As for all peptides a very low selectivity between bacterial and eukaryotic cells was observed, we performed a detailed biophysical characterization of the interaction of one of these peptides with liposomes mimicking bacterial and eukaryotic membranes. Our results show a surface binding on the DPPC/DPPG vesicles, coupled with lipid domain formation, and, above a threshold concentration, a deep insertion into the bilayer hydrophobic core. On the contrary, mainly surface binding of the peptide on the DPPC bilayer was observed. These observed differences in the peptide interaction with the two model membranes suggest a divergence in the mechanisms responsible for the antimicrobial activity and for the observed high toxicity toward mammalian cell lines. These results could represent an important contribution to unravel some open and unresolved issues in the development of synthetic CAMPs.
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影响因子：
4.9
作者：
Kasetty, Gopinath;Papareddy, Praveen;Schmidtchen, Artur
通讯作者：
Schmidtchen, Artur
影响因子：
2.9
作者：
Henzler-Wildman, KA;Martinez, GV;Ramamoorthy, A
通讯作者：
Ramamoorthy, A
影响因子：
3.4
作者：
Imura, Yuichi;Choda, Naoki;Matsuzaki, Katsumi
通讯作者：
Matsuzaki, Katsumi
影响因子：
3.7
作者：
den Hertog, Alice L.;van Marle, Jan;Amerongen, Arie V. Nieuw
通讯作者：
Amerongen, Arie V. Nieuw
影响因子：
3.4
作者：
Busi, Elena;Vitiello, Giuseppe;D'Errico, Gerardino
通讯作者：
D'Errico, Gerardino