Engineered Assemblies from Constitutionally Isomeric Peptides Modulate Antimicrobial Activity

Area of Science:

• Biochemistry
• Molecular Biology
• Materials Science

Background:

• Antimicrobial peptides (AMPs) are crucial in combating multidrug-resistant bacteria.
• The link between AMP molecular design, structure, and antibacterial efficacy requires further elucidation.

Purpose of the Study:

• To investigate how subtle molecular design changes in AMPs affect their assembled structures and antibacterial activity.
• To explore the potential of rationally designed AMPs as alternatives to conventional antibiotics.

Main Methods:

• Synthesis and characterization of constitutionally isomeric AMPs.
• Spectroscopic analysis and molecular dynamics simulations to study molecular packing and surface charges.
• In vitro antibacterial assays against methicillin-resistant *Staphylococcus aureus* (MRSA).

Main Results:

• Constitutionally isomeric AMPs self-assembled into filaments with similar dimensions.
• Minor amino acid positional changes significantly altered molecular packing and surface charge.
• All AMPs demonstrated activity against MRSA, with efficacy varying based on molecular design.
• AMPs exhibited good biocompatibility with eukaryotic cells.

Conclusions:

• Rational molecular design is a viable strategy to tune AMP bioactivity and assembled structures.
• These AMPs show promise as potential antibacterial agents against resistant pathogens.
• Understanding structure-activity relationships is key to developing novel AMP-based therapeutics.