Multivalent Fucose Derivatives Block Aspergillus Lectin AFL

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Solution Overview

Problem

Current treatments for aspergillosis, caused by Aspergillus spp., face challenges such as toxicity and resistance to antifungal agents, with limited effectiveness of existing drugs like azole derivatives, amphotericin B, and echinocandins, and inhalation therapies posing long-term toxicity concerns.

Innovation Solution

Development of multivalent fucose derivatives with specific molecular weights (0.6 to 340 kDa) that target and block the Aspergillus spp. lectin AFL, preventing fungal adhesion to host cells, offering a prophylactic and therapeutic solution for infections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If azole derivatives are used to treat aspergillosis, then antifungal activity is achieved, but resistance (innate or acquired) develops

Engineering Contradiction:

Improveantifungal activityVSAvoidresistance

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention changes the molecular parameters of the antifungal agent by using multivalent fucose derivatives with specific molecular weights (0.6 to 340 kDa) and multiple fucose moieties, thereby achieving antifungal activity through a different mechanism that avoids resistance

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention segments the antifungal approach by targeting specific lectin-carbohydrate interactions rather than using broad-spectrum antifungals, using multiple fucose moieties to block specific adhesion sites on Aspergillus spores

Inventive Principle:

Principle #1Segmentation

2Adaptability or versatility

If amphotericin B is used for broad spectrum antifungal treatment, then broad spectrum activity is achieved, but renal toxicity occurs

Engineering Contradiction:

Improvebroad spectrum activityVSAvoidrenal toxicity

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The invention applies local quality by designing fucose derivatives with specific molecular weights and valencies that target Aspergillus lectins specifically, rather than using broad-spectrum agents, thereby achieving selective antifungal activity with reduced toxicity

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The fucose derivatives act as intermediaries that block the lectin-carbohydrate interaction, preventing fungal adhesion without the toxic effects of broad-spectrum antifungals like amphotericin B

Inventive Principle:

Principle #24Intermediary (Mediator)

3Adaptability or versatility

If echinocandins are used as antifungal treatment, then new class activity is achieved, but activity on Aspergillus spp. is insufficient

Engineering Contradiction:

Improvenew class activityVSAvoidactivity on Aspergillus spp.

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The invention changes the chemical parameters by using fucose derivatives with specific molecular weights (0.6 to 340 kDa) and multiple fucose moieties, achieving reliable activity on Aspergillus spp. through a mechanism distinct from echinocandins

Inventive Principle:

Principle #35Parameter changes

4Ease of operation

If inhalation of antifungals is used as therapeutic alternative, then local treatment is achieved, but long-term toxicity occurs

Engineering Contradiction:

Improvelocal treatmentVSAvoidlong-term toxicity

Core Design Contradiction:

Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The invention uses multivalent fucose derivatives as short-acting, low-toxicity agents that can be administered locally via inhalation, providing prophylaxis and treatment without the long-term toxicity concerns of traditional inhaled antifungals

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

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 multivalent fucose derivatives effectively prevent and treat Aspergillus spp. infections by inhibiting the fungal adhesion to host cells, providing a safer and more effective alternative to existing treatments by targeting the Aspergillus spp. lectin AFL.

Implementation Method 1

The present Invention is based on the unexpected blocking of the Aspergillus spp lectin AFL by the compound of the Invention. This lectin is found on the surface of the Aspergillus spp spores and allows the fungus to adhere on the glycans of the host cells

Methodology Applied

Scientific EffectLectin-carbohydrate binding: Adsorption

Data Source

PatentUS11389466B2Multivalent fucose derivatives for use as a drug

Publication Date: 2022.07.19 UNIV DE NANTES

AI summary

Disclosed is a compound bearing at least two fucose moieties for its use as a drug in the prevention or treatment of infections caused by Aspergillus spp, the compound having a molecular weight included from 0.6 to 340 kDa, in particular from 0.6 to 2 kDa or from 1 to 7 kDa or from 2 to 10 kDa or from 5 to 340 kDa.