Antimicrobial Peptide Synthesis Reducing Toxicity and Cost

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Solution Overview

Problem

Current antimicrobial peptides (AMPs) face challenges due to high in vivo toxicity, liability towards proteases, and high manufacturing costs, as well as complexity in synthesis, limiting their clinical use against both drug-sensitive and drug-resistant bacteria.

Innovation Solution

Development of compounds comprising an aromatic radical and/or aliphatic radical, an alkyl amine, and an amino acid moiety, synthesized through a method involving Schiff's base formation and tert-butoxy carbamate protection, to create potent antimicrobial agents effective against both drug-sensitive and drug-resistant bacteria with reduced toxicity and simplified synthesis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If natural antimicrobial peptides are used, then antimicrobial activity is achieved, but in vivo toxicity increases

Engineering Contradiction:
Improveantimicrobial activityVSAvoidin vivo toxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the chemical structure of antimicrobial peptides by changing parameters such as amino acid composition, peptide length, and side chain modifications to reduce toxicity while preserving antimicrobial activity. This is achieved through systematic variation of peptide sequences and chemical properties to optimize the activity-toxicity ratio.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates composite or hybrid peptide structures that combine different amino acid sequences and chemical moieties to achieve both antimicrobial efficacy and reduced toxicity. These composite peptides integrate functional domains that target bacterial cells specifically while minimizing interaction with host cells.

Inventive Principle:
Principle #40Composite materials

2Reliability

If natural antimicrobial peptides are used, then antimicrobial activity is achieved, but manufacturing cost increases

Engineering Contradiction:
Improveantimicrobial activityVSAvoidmanufacturing cost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent employs inexpensive amino acid building blocks and readily available chemical reagents for peptide synthesis. The simplified synthetic routes use common laboratory chemicals and standard peptide coupling methods, making the manufacturing process more cost-effective compared to natural extraction or complex biosynthetic approaches.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention optimizes synthesis parameters including reaction conditions, purification methods, and peptide length to reduce manufacturing complexity and cost. By controlling peptide length and amino acid composition, the synthesis process becomes more efficient and economically viable.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If natural antimicrobial peptides are used, then antimicrobial activity is achieved, but synthesis complexity increases

Engineering Contradiction:
Improveantimicrobial activityVSAvoidsynthesis complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent divides the peptide synthesis into modular segments or building blocks that can be assembled systematically. This segmentation allows for stepwise construction of the antimicrobial peptide, simplifying the overall synthesis process and enabling easier optimization of each individual component.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention simplifies synthesis complexity by optimizing peptide length and amino acid sequence parameters to avoid complex post-translational modifications and folding requirements. The designed peptides have simplified structures that are more amenable to chemical synthesis while retaining biological activity.

Inventive Principle:
Principle #35Parameter changes

4Ease of manufacture

If conventional antibiotics are used, then ease of manufacture is improved, but bacterial resistance develops

Engineering Contradiction:
Improveease of manufactureVSAvoideffectiveness against resistant bacteria
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

Instead of targeting intracellular bacterial processes like conventional antibiotics, the patent employs antimicrobial peptides that act on the bacterial cell membrane from the outside. This inverted mechanism of action—lysis of the cell membrane rather than intracellular target inhibition—bypasses traditional resistance mechanisms and maintains effectiveness against resistant strains.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The patent uses short-lived, rapidly acting antimicrobial peptides that cause immediate cell membrane disruption. This rapid action prevents bacteria from developing resistance, as the peptides act faster than the bacteria can mount a defensive response or undergo mutation.

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 compounds exhibit significant antibacterial activity against various bacteria, including drug-resistant strains, with lower toxicity and cost-effectiveness, offering a promising alternative to traditional antibiotics.

Implementation Method 1

reacting aldehyde of aromatic radical with an alkyl amine to obtain a Schiff's base

Methodology Applied
Scientific EffectSchiff's base formation: Chemical Bonding

Implementation Method 2

reducing the Schiff's base to obtain a secondary amine

Methodology Applied
Scientific EffectReduction: Reduction

Implementation Method 3

reacting the secondary amine with a free acid group of tert-butoxy carbamate protected amino acid

Methodology Applied
Scientific EffectProtecting group chemistry: Chemical Bonding

Data Source

PatentEP2934563B1Antimicrobial compounds, their synthesis and applications thereof
Publication Date: 2020.07.08 JAWAHARLAL NEHRU CENT FOR ADVANCED SCI RES
  • EP2934563B1 patent drawingFigure 1
  • EP2934563B1 patent drawingFigure 2
  • EP2934563B1 patent drawingFigure 2

AI summary

The present disclosure relates to the field of medicinal chemistry and more particularly to the development of antimicrobial compounds. The disclosure relates to the synthesis and characterization of compounds comprising aromatic radical or an aliphatic radical, an alkyl amine and amino acid moiety wherein said compounds exhibit antimicrobial activity against various drug-sensitive and drug-resistant pathogenic 10 microorganisms.