STAMPs Target Peptides for Selective Pathogen Killing

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Solution Overview

Problem

Current antimicrobial therapies for mucosal infections are ineffective due to broad-spectrum activity that harms benign microflora, leading to antibiotic-associated infections and the emergence of drug-resistant pathogens, necessitating targeted therapies that selectively kill pathogens without affecting normal flora.

Innovation Solution

Development of selectively targeted antimicrobial peptides (STAMPs) comprising a targeting peptide linked to an antimicrobial peptide via a peptide linker, specifically designed to recognize and bind to target microbial organisms, enhancing killing potency and selectivity while minimizing impact on benign microflora.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If broad-spectrum antibiotics are used to treat mucosal infections, then pathogen killing efficacy is improved, but harm to benign microflora increases

Engineering Contradiction:
Improvepathogen killing efficacyVSAvoidharm to benign microflora
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The antimicrobial agent is segmented into two functional components: a targeting peptide that specifically recognizes and binds to pathogen surface markers, and an antimicrobial peptide that kills the pathogen. This segmentation allows the targeting function to be optimized for specificity while the antimicrobial function provides efficacy, resolving the contradiction between killing pathogens and preserving benign microflora.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The targeting peptide confers local quality by providing specific recognition and binding to pathogen surface markers (such as lipoteichoic acid in Gram-positive bacteria). This localized targeting ensures that the antimicrobial activity is concentrated at the pathogen-cell interface, enhancing pathogen killing while minimizing off-target effects on benign microflora that lack these specific markers.

Inventive Principle:
Principle #3Local quality

2Reliability

If conventional antibiotics are prescribed for mucosal infections, then infection treatment is achieved, but antibiotic-associated infections increase

Engineering Contradiction:
Improveinfection treatmentVSAvoidantibiotic-associated infections
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

By segmenting the therapeutic agent into a targeting peptide and an antimicrobial peptide, the system achieves specific pathogen targeting without the broad-spectrum effects of conventional antibiotics. This reduces the disruption to normal mucosal flora, thereby preventing antibiotic-associated infections while maintaining effective treatment of the primary infection.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the spectral parameters of antimicrobial activity from broad-spectrum to narrow-spectrum by incorporating the targeting peptide. This parameter change in specificity allows effective treatment of mucosal infections while avoiding the collateral damage to beneficial flora that causes antibiotic-associated infections.

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If wide-spectrum antibiotics are used, then pathogen coverage is improved, but emergence of drug-resistant strains is promoted

Engineering Contradiction:
Improvepathogen coverageVSAvoiddrug resistance
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The targeting peptide segment provides specific recognition of pathogen surface markers, enabling coverage of particular pathogen types without the need for broad-spectrum activity. This segmented approach maintains adaptability to specific pathogens while avoiding the selective pressure that drives drug-resistant strain emergence associated with wide-spectrum antibiotics.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The targeting peptide imparts local quality by providing specific binding to pathogen surface structures. This localized targeting mechanism allows effective pathogen coverage for specific diseases while avoiding the non-specific effects that promote drug resistance, as the antimicrobial peptide is only activated at the specific pathogen-target interface.

Inventive Principle:
Principle #3Local quality

4Manufacturing precision

If targeted antimicrobial peptides are developed, then selectivity against pathogens is improved, but manufacturing complexity increases

Engineering Contradiction:
Improveselectivity against pathogensVSAvoidmanufacturing complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The targeting peptide and antimicrobial peptide are merged into a single chimeric molecule through covalent bonding. This merging simplifies the manufacturing process by eliminating the need to produce and combine two separate agents, while maintaining the selectivity and efficacy of the targeted antimicrobial peptide therapy.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The chimeric peptide structure provides multi-functionality: the targeting peptide domain provides specific pathogen recognition, while the antimicrobial peptide domain provides killing activity. This universal design approach allows a single molecule to perform multiple functions, simplifying manufacturing compared to producing separate targeted and antimicrobial agents.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentEP2061488B1Selectively targeted antimicrobial peptides and the use thereof
Publication Date: 2014.07.30 C3 JIAN
  • EP2061488B1 patent drawingFigure 1
  • EP2061488B1 patent drawingFigure 2A~2C
  • EP2061488B1 patent drawingFigure 3

AI summary

The present invention relates to targeting peptides capable of specifically binding to microbial organisms (e.g., P. aeruginosa or S. mutans), antimicrobial peptides having antimicrobial activities, and specifically/selectively targeted antimicrobial peptides (STAMPs). In addition, the present invention provides methods of selectively killing or inhibiting microbial organisms by using the peptides or compositions provided by the present invention.