Hexatoxin Peptide Variants Alkaline pH Stability

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Solution Overview

Problem

Spider-derived pesticidal peptides face challenges in stability at alkaline pH, leading to reduced efficacy and practical application limitations, particularly due to rapid degradation and resistance development in pests.

Innovation Solution

Development of novel hexatoxin peptide variants with specific amino acid modifications that maintain biological activity and enhance stability at alkaline pH, allowing for improved storage, formulation, and application in biopesticides.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If spider-derived pesticidal peptides are used for pest control, then pesticidal activity is achieved, but stability at alkaline pH deteriorates leading to rapid degradation

Engineering Contradiction:
Improvepesticidal activityVSAvoidstability at alkaline pH
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by systematically modifying amino acid residues at specific positions (N27, N28, N29, N30, N31, N32) in the hexatoxin peptide sequence. These positional parameter changes alter the peptide's chemical properties to enhance alkaline pH stability while preserving pesticidal activity against resistant pest populations.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements local quality by introducing specific amino acid substitutions at defined positions within the peptide sequence rather than uniform modification throughout. This localized modification approach targets specific regions of the peptide to improve alkaline stability while maintaining the overall structural integrity and biological function of the toxin.

Inventive Principle:
Principle #3Local quality

2Ease of operation

If peptides are stored in solution at higher temperatures, then ease of storage is improved, but stability deteriorates with degradation within a week at 4°C

Engineering Contradiction:
Improveease of storageVSAvoidsolution stability
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The modified hexatoxin peptides exhibit altered thermal and pH stability parameters compared to native peptides. The amino acid substitutions at positions N27-N32 confer enhanced resistance to thermal degradation and pH-induced hydrolysis, allowing storage at higher temperatures and in alkaline conditions without rapid degradation.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If conventional biopesticides are applied, then pest control is achieved, but resistance development in pests worsens over time

Engineering Contradiction:
Improvepest control efficacyVSAvoidresistance development
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces specific amino acid variations at defined positions in the hexatoxin sequence, creating localized structural differences that enable the peptide to bind to and inhibit acetylcholinesterase in resistant pest populations. This local modification strategy allows the toxin to overcome resistance mechanisms that have developed against conventional biopesticides.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

By systematically altering amino acid residues at positions N27-N32, the patent creates peptide variants with modified molecular properties that can interact with target sites in resistant pests. These parameter changes in the peptide structure enable it to maintain efficacy against pest populations that have developed resistance to standard biopesticides.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS20240076327A1Pesticidal hexatoxin polypeptides and methods of use thereof
Publication Date: 2024.03.07 SYNGENTA CROP PROTECITON AG

AI summary

The present invention relates to a hexatoxin peptide variant comprising a. an amino acid sequence which is at least 90% identical to any one of SEQ ID NOs: 27 to 29, wherein the amino acid sequence has at least one amino acid variant on position N27; b. an amino acid sequence which is at least 90% identical to any one of SEQ ID NOs: 2, 6, 7, 30 or 32, wherein the amino acid sequence has at least one amino acid variant on position N28; c. an amino acid sequence which is at least 90% identical to any one of SEQ ID NOs: 1, 3, 4, 5, 8 to 24 or 31, wherein the amino acid sequence has at least one amino acid variant on position N29; d. an amino acid sequence which is at least 90% identical to SEQ ID NO: 25, wherein the amino acid sequence has at least one amino acid variant on position N30; e. an amino acid sequence which is at least 90% identical to SEQ ID NOs: 26, wherein the amino acid sequence has at least one amino acid variant on position N31; or f. an amino acid sequence which is at least 90% identical to SEQ ID NO: 34, wherein the amino acid sequence has at least one amino acid variant on position N32; each of which retain the biological activity of the hexatoxin; with the proviso that the peptide does not comprise the amino acid sequence of SEQ ID NO: 33.