Antimicrobial Peptoids with Altered Helical Folding for Selective Bacterial Activity

Solution Overview

Problem

Existing antimicrobial peptides are rapidly degraded in vivo and exhibit cytotoxicity against animal cells, limiting their clinical application, especially against multidrug-resistant bacteria.

Innovation Solution

Development of antimicrobial peptoids with altered helical structure or charge characteristics, which are more stable and less toxic to animal cells, using specific formulas such as H-Nlys-Npm-Npm-Nlys-Nspe-Npm-(Nlys-Npm-Npm)2-NH2, to enhance selectivity and efficacy against bacteria.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If natural antimicrobial peptides are used to treat bacterial infections, then excellent antimicrobial activity against multidrug-resistant bacteria is achieved, but they are rapidly degraded by enzymes in vivo and exhibit cytotoxicity against animal cells

Engineering Contradiction:

Improveantimicrobial activityVSAvoidstability in vivo

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent creates peptoid copies that mimic the structure and function of natural antimicrobial peptides. These peptoids are N-substituted glycine oligomers that replicate the cationic and amphipathic characteristics of natural peptides, enabling them to maintain antimicrobial activity while being resistant to enzymatic degradation in vivo

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent systematically varies parameters such as chain length, N-terminal modifications, side chain composition, and charge density of peptoids to optimize the balance between antimicrobial activity and cytotoxicity. By adjusting these parameters, the peptoids achieve enhanced stability and selectivity compared to natural peptides

Inventive Principle:

Principle #35Parameter changes

2Reliability

If the dose of natural antimicrobial peptides is increased to overcome degradation, then antimicrobial efficacy may be improved, but toxicity to animal cells increases

Engineering Contradiction:

Improveantimicrobial efficacyVSAvoidcytotoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The peptoids are designed as stable, non-degradable alternatives to natural peptides, effectively replacing the need for high doses that would otherwise be required to compensate for rapid peptide degradation. This substitution eliminates the dose-dependent cytotoxicity problem while maintaining antimicrobial efficacy

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent introduces specific local modifications to the peptoid structure, such as N-terminal acetylation or other capping groups, and selective side chain compositions that enhance selectivity for bacterial cells over mammalian cells. These localized modifications reduce cytotoxicity while preserving antimicrobial activity

Inventive Principle:

Principle #3Local quality

3Stability of the object's composition

If existing antimicrobial peptoids are developed with modified peptide backbones, then resistance against proteolysis is increased, but cytotoxicity against mammalian cells such as NIH 3T3 mouse fibroblasts remains a problem

Engineering Contradiction:

Improveresistance against proteolysisVSAvoidcytotoxicity against mammalian cells

Core Design Contradiction:

Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent systematically varies parameters such as chain length, N-terminal modifications, side chain composition, and charge density of peptoids to optimize the balance between antimicrobial activity and cytotoxicity. By adjusting these parameters, the peptoids achieve enhanced stability and selectivity compared to natural peptides

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces specific local modifications to the peptoid structure, such as N-terminal acetylation or other capping groups, and selective side chain compositions that enhance selectivity for bacterial cells over mammalian cells. These localized modifications reduce cytotoxicity while preserving antimicrobial activity

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS10815275B2Antimicrobial peptoids with improved selectivity and use thereof

Publication Date: 2020.10.27 GWANGJU INST OF SCI & TECH

AI summary

Antimicrobial peptoids with improved selectivity to bacteria and a use thereof are described. Specifically, the antimicrobial peptoids have high antimicrobial activity and greatly decreased toxicity to animal cells. The antimicrobial peptoids show excellent antimicrobial activity against bacteria and exhibit low cytotoxicity to animal cells due to altered degree of folding in helical structure or altered charge characteristics. Therefore, the antimicrobial peptoids have improved selectivity to bacteria, and thus can be usefully used as antimicrobial compositions.