Antimicrobial properties of enzymatically triggered self-assembling aromatic peptide amphiphiles

Area of Science:

• Biochemistry
• Materials Science
• Synthetic Biology

Background:

• Catalysis and self-assembly are crucial in biological systems.
• Synthetic analogues can potentially direct biological processes.
• Enzyme-triggered assembly of peptide derivatives can induce bacterial cell death via intracellular fiber formation.

Purpose of the Study:

• To investigate the self-assembly of phosphorylated 9-fluorenylmethyloxycarbonyl (Fmoc) protected dipeptide amphiphiles.
• To design alkaline phosphatase-responsive precursors for controlled self-assembly.
• To evaluate the in vivo conversion and antimicrobial activity of these peptide amphiphiles.

Main Methods:

• Synthesis of phosphorylated Fmoc-dipeptide amphiphiles.
• In vitro characterization using microscopy, fluorescence, and FTIR.
• In vivo studies involving enzyme overexpression in E. coli.
• Antimicrobial activity assays.

Main Results:

• Distinct self-assembly behaviors were observed in vitro: fiber formation for FY, YT, YS, YN, and spherical structures for YQ.
• Successful in vivo conversion of precursors to self-assembling aromatic peptide amphiphiles was demonstrated.
• All tested aromatic peptide amphiphiles exhibited a similar antimicrobial response.

Conclusions:

• Phosphorylated peptide amphiphiles can be designed for enzyme-responsive self-assembly.
• Controlled self-assembly and antimicrobial activity can be achieved in vivo.
• The study highlights the potential of synthetic peptide amphiphiles in directing biological processes.