Cationic Peptoid Copolymers for Selective Antimicrobial Activity

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Solution Overview

Problem

Current antimicrobial peptides (AMPs) face limitations such as toxicity, nonspecificity, susceptibility to proteolysis, costly production, and challenges in targeted delivery, which hinder their development as effective therapeutic agents against drug-resistant bacteria.

Innovation Solution

Development of cationic peptoid/N-substituted peptidic copolymers with antimicrobial activity, synthesized through a process involving N-carboxyanhydride monomers, which allows for the creation of polymers with controlled cationic content and topology, enhancing specificity and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If native antimicrobial peptides (AMPs) are used for therapeutic treatment, then broad antimicrobial activity is achieved, but toxicity to human cells (hemolysis) occurs

Engineering Contradiction:

Improveantimicrobial activityVSAvoidtoxicity to human cells

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention segments the AMP structure into distinct functional domains: a cationic antimicrobial domain and a non-cationic structural domain. This segmentation allows the cationic content to be controlled at specific positions (N-terminal or side chains) while the rest of the structure provides stability and specificity, thereby reducing non-specific toxicity to human cells while maintaining antimicrobial activity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention applies local quality by concentrating cationic charges only in specific regions of the peptide (N-terminal region or side chains of specific amino acids) rather than distributing them uniformly throughout the structure. This localized cationic content provides the necessary antimicrobial activity while the non-cationic portions maintain structural integrity and reduce non-specific interactions with human cells.

Inventive Principle:

Principle #3Local quality

2Reliability

If high concentrations of AMPs are administered to achieve therapeutic effect, then antimicrobial efficacy is improved, but cost increases and toxic side effects worsen

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidtoxic side effects

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The invention changes key parameters of the AMP structure, specifically the cationic content and amino acid composition, to optimize the therapeutic window. By controlling the number and position of cationic residues and incorporating specific structural motifs, the peptides achieve enhanced antimicrobial activity at lower concentrations, reducing both cost and toxic side effects.

Inventive Principle:

Principle #35Parameter changes

3Quantity of substance

If solid state peptide synthesis or cell culture production is used for AMP manufacturing, then AMP production is achieved, but cost and time consumption increase

Engineering Contradiction:

ImproveAMP productionVSAvoidproduction cost and time

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The invention employs peptides with optimized sequences that can be produced using more economical methods. The specific amino acid compositions and structural features described enable production through cost-effective approaches while maintaining stability and activity, reducing reliance on expensive solid state synthesis or lengthy cell culture processes.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

4Ease of operation

If AMPs are administered orally or systemically, then delivery to infection site is attempted, but rapid degradation by proteolysis or immune system clearance occurs

Engineering Contradiction:

Improvedelivery methodVSAvoidstability in circulation

Core Design Contradiction:

Ease of operationVSDuration of action of stationary object

Solution Approach 1:

The invention incorporates structural modifications and protective groups that pre-protect the peptide from proteolytic degradation before administration. The specific amino acid selections and structural motifs provide resistance to proteases, allowing the peptide to survive gastrointestinal passage or systemic circulation long enough to reach the infection site.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention creates composite peptide structures combining cationic antimicrobial domains with non-cationic structural domains that provide enhanced stability. This composite structure resists proteolysis and immune system clearance while maintaining the antimicrobial function, enabling oral or systemic administration.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS20240189486A1Antimicrobial cationic peptoid and n-subtituted peptidic copolymers, preparation and uses thereof

Publication Date: 2024.06.13 UNIVERSITE DE BORDEAUX

AI summary

The present invention provides cationic peptoid/N-substituted peptidic copolymers, and pharmaceutical compositions thereof, as described generally and in subclasses herein, which compounds are useful for the treatment of microbial infections.