Heparin-binding cationic peptide self-assembling peptide amphiphiles useful against drug-resistant bacteria
Inventors
CHANG, Run • Subramanian, Keerthana • Wang, Mian • Webster, Thomas J.
Assignees
Northeastern University Boston
Publication Number
US-12319752-B2
Publication Date
2025-06-03
Expiration Date
2037-12-05
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Abstract
Disclosed are peptides comprising an amphiphilic backbone and a cationic heparin-binding motif peptide. The peptides can be used in methods of antimicrobial treatment.
Core Innovation
The invention provides peptides comprising an amphiphilic backbone and a cationic heparin-binding motif peptide, specifically described as self-assembling peptide amphiphiles. These polypeptides can self-assemble into nanostructures such as nanorods or nanofibers, presenting a cationic Cardin motif on the surface. The self-assembly is driven by non-covalent intermolecular forces, including hydrophobic interactions from an alkyl or alkenyl tail and the formation of β-sheet secondary structure in the backbone.
This technology addresses the problem of bacterial antibiotic resistance, which is a significant threat to global health. Existing antibiotics often become ineffective due to the rapid emergence of resistance in both Gram-positive and Gram-negative bacteria. The need exists for novel antibacterial agents that target a broad range of bacteria, including drug-resistant strains, without promoting further resistance.
The self-assembling peptide amphiphiles described herein function by disrupting bacterial cell membranes through non-specific electrostatic and hydrophobic interactions. In these systems, the heparin-binding Cardin-motif serves to initiate attachment to anionic bacterial membranes, facilitating membrane disruption and cell lysis. In contrast to free Cardin-motif peptides or peptides lacking self-assembly capability, the disclosed self-assembled nanorods exhibit potent antibacterial activity, including against antibiotic-resistant bacteria such as MRSA and multidrug-resistant E. coli.
Claims Coverage
The patent has one independent claim, which introduces a method involving specific peptide amphiphiles for preventing or suppressing bacterial growth on surfaces.
Method for preventing or suppressing bacterial growth on a surface using specific self-assembling peptide amphiphiles
A method comprising applying to a surface a plurality of polypeptides represented by: R1-y1-y2 wherein: - R1-y1 is an amphiphilic backbone; R1 is an alkyl or alkenyl group; - y1 has the sequence V4K4 (SEQ ID NO: 1) or V4K4G (SEQ ID NO: 4); - y2 is a cationic heparin-binding Cardin motif peptide; thereby preventing or suppressing growth of a bacterium on the surface.
The independent claim focuses on the application of specified self-assembling amphiphilic peptides with a heparin-binding Cardin motif for antimicrobial surface treatment, defining the structure and function critical to the inventive method.
Stated Advantages
The self-assembled ACA nanorods target the entire bacterial cell membrane via non-specific interactions, reducing development of drug resistance.
The self-assembling peptide amphiphiles exhibit broad-spectrum antibacterial activity, effective against both Gram-positive and Gram-negative bacteria, including antibiotic-resistant strains.
Production of the peptide building blocks can be achieved at large scale and low cost through bioprocessing or solid-phase synthesis.
These materials are biodegradable, lowering risk of systemic toxicity due to particle retention.
Preparation of self-assembled nanorods is simple and does not require complex chemical synthesis.
The antibacterial effect against Gram-negative bacteria is greatly enhanced upon peptide self-assembly.
Polypeptides show selective toxicity for bacteria over mammalian cells at effective concentrations.
Documented Applications
Method of preventing or suppressing microbial growth on a surface by applying the self-assembling peptide amphiphiles.
Method of antimicrobial treatment by adding the self-assembling peptide amphiphiles to a sample containing microorganisms to kill or inhibit their growth.
Preparation of self-assembled nanorods from lyophilized peptides in a suitable solvent for use as antibacterial agents.
Use as coatings on articles such as filters, membranes, packing materials (for foods, agriculture, paints), flow cells, filter gaskets, gloves, masks, garments, wound dressings, implants, catheters, and other medical devices to prevent or suppress microbial growth.
Direct application to eye infections as eye drops or as rinsing solutions for contact lenses using the self-assembled nanoparticles in solution.
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