FadA-Binding Peptides to Block Colorectal Carcinogenesis
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Solution Overview
Problem
Current treatments for colorectal cancer, such as surgical interventions, radiotherapy, and chemotherapy, are inadequate, and the use of antibiotics to combat Fusobacterium nucleatum infections leads to antibiotic resistance, necessitating a receptor-specific approach to inhibit bacteria-cell interactions to prevent carcinogenesis and infections in cancer patients.
Innovation Solution
Development of ten peptide sequences with binding energies greater than −11.6 kcal/mol that inhibit the interaction of the FadA protein from Fusobacterium nucleatum with E-cadherin, utilizing peptides with anti-cancer and antimicrobial properties, which can be conjugated with other molecules or integrated into carrier systems to prevent carcinogenesis and infections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If antibiotics are used to combat Fusobacterium nucleatum infections, then bacterial infections are suppressed, but antibiotic resistance develops
Solution Approach 1:
The patent uses peptide molecules as intermediary substances that specifically bind to the FadA protein on bacterial surfaces, blocking the bacteria's ability to interact with host cells. This peptide mediator prevents bacterial adhesion and invasion without killing the bacteria, thereby avoiding the selection pressure that leads to antibiotic resistance while still effectively suppressing the infection
Solution Approach 2:
The patent replaces the mechanical killing action of antibiotics with a molecular recognition and blocking mechanism. The peptides use specific molecular interactions (binding to FadA protein) to prevent bacterial pathogenesis rather than relying on broad-spectrum antimicrobial killing, which reduces the development of resistance
2Object-affected harmful factors
If broad-spectrum antibiotics are used to prevent F. nucleatum role in colorectal cancer, then bacterial activity is inhibited, but carcinogenesis effect becomes more aggressive
Solution Approach 1:
The patent applies local quality by designing peptides with specific sequences that target only the FadA protein on F. nucleatum bacteria. This localized, specific binding blocks the bacteria's ability to promote carcinogenesis through E-cadherin interaction without the broad-spectrum effects of antibiotics that can disrupt microbiota and potentially worsen carcinogenesis
Solution Approach 2:
The peptides act as intermediary molecules that specifically interfere with the FadA-E-cadherin interaction pathway. By blocking this specific molecular interaction, the peptides prevent the bacteria-mediated activation of WNT/β-catenin signaling and carcinogenesis without using broad-spectrum antibiotics that could have harmful side effects
3Object-affected harmful factors
If silver nanoparticles are used as cationic agents, then antimicrobial activity is achieved, but off-target side effects and liver toxicity increase
Solution Approach 1:
The patent uses peptide molecules as specific intermediaries that bind to bacterial surface proteins (FadA) with high affinity. This specific molecular recognition allows the peptides to target bacteria precisely without the non-specific cellular uptake and liver accumulation that occurs with silver nanoparticles, thereby avoiding off-target side effects and hepatotoxicity
Solution Approach 2:
The patent replaces the non-specific physical-chemical action of silver nanoparticles (ionic interactions, membrane disruption) with specific biological recognition mechanisms. The peptides use sequence-specific binding to FadA protein to achieve antimicrobial activity with high target specificity, eliminating the off-target effects and liver toxicity associated with nanoparticle accumulation
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The peptides effectively inhibit FadA protein-mediated tumorigenesis and bacterial infections, offering a biocompatible solution with flexible interaction capabilities to activate or suppress specific molecular pathways, enhancing treatment efficacy for colorectal cancer and reducing antibiotic resistance.
Implementation Method 1
The binding energy of the peptides to the FadA protein was calculated to be greater than −11.6 kcal/mol using molecular docking analysis
Data Source
AI summary
Peptides for use in systems that prevent the interaction of the FadA protein released from the Fusobacterium nucleatum (F. nucleatum) bacterium with E-cadherin, which has a carcinogenic effect, or the inhibition of the microorganism with antimicrobial agents and that will inhibit the carcinogenesis mechanisms of F. nucleatum infection and enable the development of therapeutic systems against infections that may occur due to the decreased immunity of patients undergoing cancer treatment with the use of peptides with anti-cancer and antimicrobial properties by developing ten peptides with FadA protein binding energy greater than −11.6 kcal/mol. Peptides with anticancer and antimicrobial properties allow the development of therapeutic systems to prevent F. nucleatum infection, to prevent cancer development after F. nucleatum infection, or to develop therapeutic systems against infections that occur due to the decreased immunity of cancer patients due to cancer treatment.