Halogenated Cyclic Peptides for Multidrug-Resistant Bacteria

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Solution Overview

Problem

There is an urgent need for new and effective antibiotics to treat infections caused by multidrug-resistant bacteria, particularly Clostridium difficile, Pseudomonas aeruginosa, and Burkholderia cepacia complex, as existing treatments are limited and often ineffective against antibiotic-resistant strains.

Innovation Solution

Development of novel non-natural cyclic peptide compounds with specific structural features, including halogen groups, which exhibit selective antibacterial activity against these pathogens without adversely affecting normal gut flora, thereby promoting a healthy gut ecosystem.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing antibiotics are used to treat multidrug-resistant bacteria, then treatment options are limited, but they fail to effectively treat antibiotic-resistant strains

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidtreatment options

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent modifies the natural argyrin peptide structure by introducing halogen substituents (fluoro, chloro, or bromo groups) at specific positions (R3, R4, R5) and varying side chain compositions. These structural parameter changes create a series of derivatives with enhanced and differentiated antibacterial activity, allowing effective treatment of multidrug-resistant strains while maintaining selectivity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention combines the natural argyrin peptide backbone with synthetic halogenated modifications to create hybrid compounds. This composite approach integrates the biological activity of natural peptides with the enhanced stability and selectivity of halogenated structures, resulting in compounds with improved therapeutic profiles

Inventive Principle:

Principle #40Composite materials

2Adaptability or versatility

If broad-spectrum antibiotics are used to treat bacterial infections, then they can treat multiple pathogens, but they adversely affect normal gut flora

Engineering Contradiction:

Improvepathogen coverageVSAvoidimpact on gut flora

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces specific halogen substitutions at defined positions (R3, R4, R5) and controls side chain composition ratios to create compounds with localized enhanced activity against specific pathogens. This local modification approach confers selective toxicity toward multidrug-resistant bacteria while sparing normal gut flora, achieving pathogen-specific treatment

Inventive Principle:

Principle #3Local quality

Data Source

PatentEP3596089B1Antibacterial compounds

Publication Date: 2023.12.06 UNIVERSITY OF NOTTINGHAM

Figure 1A~1B
Figure 2A~2C
Figure 3~4B

AI summary

Novel compounds having antimicrobial activitiy, in particular against Pseudomonas aeruginosa, Burkholderia cepaciaand/or Clostridium difficile, and a pharmaceutical composition containing the novel compound.