Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University , Ankara 06800, Turkey.
Neuroscience Graduate Program, Bilkent University , Ankara 06800, Turkey.
Mol Pharm. 2017 Nov 6;14(11):3660-3668. doi: 10.1021/acs.molpharmaceut.7b00434. Epub 2017 Oct 19.
Noncovalent and electrostatic interactions facilitate the formation of complex networks through molecular self-assembly in biomolecules such as proteins and glycosaminoglycans. Self-assembling peptide amphiphiles (PA) are a group of molecules that can form nanofibrous structures and may contain bioactive epitopes to interact specifically with target molecules. Here, we report the presentation of cationic peptide sequences on supramolecular nanofibers formed by self-assembling peptide amphiphiles for cooperative enhanced antibacterial activity. Antibacterial properties of self-assembled peptide nanofibers were significantly higher than soluble peptide molecules with identical amino acid sequences, suggesting that the tandem presentation of bioactive epitopes is important for designing new materials for bactericidal activity. In addition, bacteria were observed to accumulate more rapidly on peptide nanofibers compared to soluble peptides, which may further enhance antibacterial activity by increasing the number of peptide molecules interacting with the bacterial membrane. The cationic peptide amphiphile nanofibers were observed to attach to bacterial membranes and disrupt their integrity. These results demonstrate that short cationic peptides show a significant improvement in antibacterial activity when presented in the nanofiber form.
非共价和静电相互作用促进了生物分子(如蛋白质和糖胺聚糖)中分子自组装形成复杂网络。自组装肽两亲物(PA)是一类可以形成纳米纤维结构的分子,可能包含生物活性表位,以与靶分子特异性相互作用。在这里,我们报告了在自组装肽两亲物形成的超分子纳米纤维上展示阳离子肽序列,以协同增强抗菌活性。自组装肽纳米纤维的抗菌性能明显高于具有相同氨基酸序列的可溶性肽分子,这表明生物活性表位的串联呈现对于设计具有杀菌活性的新材料很重要。此外,与可溶性肽相比,观察到细菌在肽纳米纤维上更快地积累,这可能通过增加与细菌膜相互作用的肽分子数量进一步增强抗菌活性。观察到阳离子肽两亲物纳米纤维附着在细菌膜上并破坏其完整性。这些结果表明,当呈纳米纤维形式时,短阳离子肽的抗菌活性显著提高。