1. Switchable modulation of bacterial growth and biofilm formation based on supramolecular tripeptide amphiphiles
Limin Chen, Dan Yang, Jie Feng, Min Zhang, Qiuping Qian, Yunlong Zhou J Mater Chem B. 2019 Oct 23;7(41):6420-6427. doi: 10.1039/c9tb00973f.
Design and fabrication of smart supramolecular peptide systems is an effective strategy to develop antibacterial agents that can be selectively activated/inactivated by external stimuli for combating bacterial resistance. In this work, we selectively synthesized isomeric tripeptides (i.e., Ala-Gly-Gly-OH and Gly-Gly-Ala-OH) with the simplest structures to construct a minimalistic dual-responsive supramolecular antibacterial system. To impart stimuli-responsiveness, the tripeptides were modified using a hydrophobic n-butylazobenzene tail at the N-terminal, which benefited the enhancement of the hydrophobicity of the tripeptides and they served as synergistic antibacterial moieties. Two different self-assembled 1-D morphologies (i.e., nanotwists and nanofibers) were observed under the same conditions when the position of the Ala residue was altered. More importantly, the supramolecular tripeptide amphiphiles exhibited a reversible assembly/disassembly process in response to different stimuli (i.e., light and host-guest chemistry). Based on the stimuli-responsiveness, the antibacterial/antibiofilm activities against either Gram-negative or Gram-positive bacteria could be reversibly modulated.
2. Sequence isomerism-dependent self-assembly of glycopeptide mimetics with switchable antibiofilm properties
Limin Chen, Jie Feng, Dan Yang, Falin Tian, Xiaomin Ye, Qiuping Qian, Shuai Wei, Yunlong Zhou Chem Sci. 2019 Jul 11;10(35):8171-8178. doi: 10.1039/c9sc00193j. eCollection 2019 Sep 21.
In biological systems, diverse amino acid sequences and functional decorations endow proteins with specific functions. Functionally modified oligopeptides are attractive building blocks to assemble stimuli-responsive biomimetic superstructures for mimicking soft structures in nature and biomaterial applications. In this work, we selectively synthesized the structurally simplest isomeric tripeptides (i.e., Ala-Gly-Gly-OH, Gly-Ala-Gly-OH and Gly-Gly-Ala-OH) to demonstrate how the subtlest change in sequence isomerism influences the self-assembly of glycopeptides. To impart self-assembly capability and stimuli-responsiveness, the isomeric tripeptides were modified with a hydrophobic n-butylazobenzene tail at the N-terminal. We observed three different self-assembled 1-D morphologies (i.e., nanotwists, nanoribbons and nanofibers) from the azobenzene-glycopeptides (AGPs) under the same conditions when the position of the Ala residue was switched. Experimental methods including transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy and circular dichroism (CD) spectroscopy were used to characterize the structural details of glycopeptide mimetic assemblies. Martini coarse-grained molecular dynamics (MD) simulations confirmed such structural observations and investigated the differences in assembly mechanisms. Furthermore, the glycopeptide mimetic assemblies showed a reversible disassembly-assembly process in response to temperature, light or host-guest chemistry, and can be used as switchable antibiofilm nanoagents.
