Antibacterial Peptide (KW)4 Membrane Disruption

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Solution Overview

Problem

Current antibiotics face challenges with antibiotic-resistant bacteria and tolerant strains, where bacteria survive antibiotic treatment and can develop further resistance, necessitating a novel antibiotic that functions independently of autolytic enzyme activity.

Innovation Solution

Development of an antibacterial and fungicidal peptide with repeated lysine and tryptophan residues, specifically (KW)4, which demonstrates high antibacterial activity against Gram-positive, Gram-negative, and antibiotic-tolerant strains, as well as fungicidal activity against pathogenic fungi, with minimal cytotoxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antibiotics are used to treat bacterial infections, then initial treatment effect is achieved, but antibiotic resistance and tolerance develop causing treatment failure

Engineering Contradiction:

Improveantibacterial efficacyVSAvoidantibiotic resistance

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the fundamental parameter of antibiotic mechanism from autolytic enzyme activation to direct membrane disruption. The peptide (KW)4 with specific amino acid sequence (Lys-Trp repeats) creates a new action mode that physically disrupts bacterial membranes through its amphipathic structure, bypassing enzymatic pathways that bacteria can resist through genetic mutation.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention uses a composite amino acid structure combining lysine (positively charged, hydrophilic) and tryptophan (hydrophobic) in a repeating pattern. This composite structure creates an amphipathic peptide that can simultaneously interact with both the hydrophilic and hydrophobic regions of bacterial membranes, enhancing membrane disruption efficacy while maintaining selectivity against bacteria versus mammalian cells.

Inventive Principle:

Principle #40Composite materials

2Reliability

If antibiotics that activate autolytic enzymes are used, then bacteria can be killed initially, but tolerant strains survive by inhibiting enzyme activity

Engineering Contradiction:

Improvebactericidal activityVSAvoidantibiotic tolerance

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the essential lethal function from the complex autolytic enzyme pathway and implements it directly through peptide-mediated membrane disruption. Instead of relying on bacterial enzymes to kill the bacteria, the (KW)4 peptide directly performs the membrane-damaging function that leads to cell death, eliminating the tolerance mechanism that depends on enzyme inhibition.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the biochemical mechanism (enzyme activation) with a physical mechanism (membrane disruption). The amphipathic peptide structure physically inserts into and disrupts the bacterial membrane through hydrophobic and electrostatic interactions, a mechanical-like process that cannot be inhibited by genetic mutations in enzymatic pathways.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Productivity

If new antibiotics are developed rapidly to overcome resistance, then treatment options increase, but development time exceeds bacterial adaptation time

Engineering Contradiction:

Improveantibiotic development rateVSAvoidresistance development time

Core Design Contradiction:

ProductivityVSLoss of time

Solution Approach 1:

Instead of continuing to develop antibiotics that target bacterial metabolic pathways (which bacteria can adapt to), the patent inverts the approach by targeting the fundamental physical structure of the bacterial membrane. This structural target is less amenable to genetic adaptation, effectively reversing the race dynamic between drug development and resistance emergence.

Inventive Principle:

Principle #13The other way round (Inversion)

4Reliability

If peptides with high antibacterial activity are designed, then efficacy against pathogens increases, but cytotoxicity to mammalian cells may increase

Engineering Contradiction:

Improveantibacterial activityVSAvoidcytotoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality differentiation through the amphipathic structure of (KW)4, where different regions of the peptide have different properties: the lysine-rich region interacts with negatively charged bacterial membrane components, while the tryptophan regions insert into the hydrophobic membrane core. This localized functional differentiation enables selective toxicity toward bacteria while sparing mammalian cells with different membrane compositions.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS10301354B2Antibacterial and fungicidal peptide in which lysine and tryptophan residues are repeated, and use thereof

Publication Date: 2019.05.28 IND ACADEMIC COOP FOUND YONSEI UNIV

AI summary

The present invention relates to an antibacterial and fungicidal peptide in which a lysine and tryptophan dipeptide is repeated. More specifically, the antibacterial and fungicidal peptide of the present invention, in which lysine and tryptophan dipeptide is repeated four times, shows excellent antibacterial activities with respect to gram-positive bacteria, gram-negative bacteria and antibiotic-resistant strains by affecting the inner membrane of harmful microorganisms, has remarkable fungicidal activities with respect to pathogenic fungi and antibiotic-resistant fungi, and shows little cytotoxicity, and thus can be useful for a pharmaceutical composition, a cosmetic composition, agricultural chemicals, a food preservative, a cosmetic preservative, and a pharmaceutical preservative.