Peptide fibrils with altered stability, activity, and cell selectivity.
Peptide fibrils with altered stability, activity, and cell selectivity.
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DOI：
10.1021/bm400618m
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发表时间：
2013-07-08
影响因子：
6.2
通讯作者：
Liang, Jun F.
中科院分区：
文献类型：
--
作者：
Chen, Long;Liang, Jun F.
与蛋白质相比，肽具有一些独特的和上级的特征。然而，肽作为治疗剂的使用受到其低稳定性和细胞选择性的阻碍。本研究构建了一个新的裂解肽（CL-1，FLGALFRALSRLL）。在生理条件下，肽CL-1自组装成动态稳定的具有纤维状结构的聚集体。与单分子CL-1和其他裂解肽相比，聚集的CL-1表现出显著改变的活性和稳定性：当与共培养的细菌和组织细胞孵育时，CL-1聚集体选择性地杀死细菌，但不伤害共培养的人细胞; CL-1聚集体在人血清中保持完整超过5小时。对脂质单层和活的人组织细胞进行的肽-细胞相互作用研究表明，与单体CL-1相比，聚集的CL-1对组织细胞的细胞亲和力和膜插入能力降低。一个动态的过程，包括聚集体的解离和重排似乎是一个必不可少的步骤，膜结合的CL-1聚集体，以实现其对组织细胞的细胞毒性。我们的研究表明，肽聚集可能是一样重要的电荷和二级结构的肽在影响肽细胞相互作用。控制肽自组装是提高生物活性肽稳定性和细胞选择性的一种新方法，具有广泛的生物医学应用前景。
Peptides have some unique and superior features compared to proteins. However, the use of peptides as therapeutics is hampered by their low stability and cell selectivity. In this study, a new lytic peptide (CL-1, FLGALFRALSRLL) was constructed. Under the physiological condition, peptide CL-1 self-assembled into dynamically stable aggregates with fibrils-like structures. Aggregated CL-1 demonstrated dramatically altered activity and stability in comparison with single molecule CL-1 and other lytic peptides: when incubated with co-cultured bacteria and tissue cells, CL-1 aggregates killed bacteria selectively but spared co-cultured human cells; CL-1 aggregates kept intact in human serum for more than five hours. Peptide-cell interaction studies performed on lipid monolayers and live human tissue cells revealed that in comparison with monomeric CL-1, aggregated CL-1 had decreased cell affinity and membrane insertion capability on tissue cells. A dynamic process involving aggregate dissociation and rearrangement seemed to be an essential step for membrane bound CL-1 aggregates to realize its cytotoxicity to tissue cells. Our study suggests that peptide aggregation could be as important as the charge and secondary structure of a peptide in affecting peptide-cell interactions. Controlling peptide self-assembly represents a new way to increase the stability and cell selectivity of bioactive peptides for wide biomedical applications.
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影响因子：
1.9
作者：
Zhang G;Yin X;Qi Y;Pendyala L;Chen J;Hou D;Tang C
通讯作者：
Tang C
影响因子：
2.9
作者：
Janek, K;Rothemund, S;Krause, E
通讯作者：
Krause, E
影响因子：
4.1
作者：
Hansel, William;Enright, Fred;Leuschner, Carola
通讯作者：
Leuschner, Carola
DOI：
10.1016/j.ejpb.2012.03.012
发表时间：
2012-06-01
影响因子：
4.9
作者：
Chen, Long;Liang, Jun F.
通讯作者：
Liang, Jun F.
影响因子：
3.7
作者：
Steinstraesser L;Hauk J;Schubert C;Al-Benna S;Stricker I;Hatt H;Shai Y;Steinau HU;Jacobsen F
通讯作者：
Jacobsen F