Derivative Peptide Sequence Optimization for Memory Function
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Solution Overview
Problem
Current methods for developing memory-improving peptides are limited by the primary structure of raw proteins, which restricts their activity and stability, and there is a need for derivatives that can effectively address oxidative stress-related memory impairments and dementia.
Innovation Solution
A high-activity memory-improving derivative peptide is developed by modifying the amino acid sequence of a pine nut-derived peptide WYPGK through enzymatic hydrolysis, separation, and structural identification, resulting in peptides like WYEGK, WYKGK, WYSGK, and WYFGK, which exhibit enhanced antioxidant activity and stability, allowing them to activate SIRT3 and improve synaptic plasticity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If enzymatic hydrolysis is used to prepare active peptides, then the peptide can be obtained from raw protein, but the functional activity is limited by the primary structure of the raw protein
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence parameters of the peptide through chemical synthesis rather than being constrained by the primary structure of raw proteins. This allows the peptide sequence to be optimized for functional activity while maintaining ease of manufacture through standardized synthesis protocols.
Solution Approach 2:
The patent creates derivative peptides that copy the basic structure of natural peptides but with modified amino acid sequences synthesized chemically. This copying approach allows replication of the peptide framework while improving functional properties that are limited in naturally occurring peptides.
2Reliability
If the amino acid sequence is modified to enhance activity, then the memory-improving and antioxidant activity increases, but the complexity of peptide synthesis increases
Solution Approach 1:
The patent segments the peptide into a core functional sequence (WYPGK) with optional modifications at specific positions. This segmentation allows the basic memory-improving activity to be maintained through the core sequence while optional modifications can be added to enhance antioxidant activity or stability, reducing the overall synthesis complexity compared to completely redesigning the peptide.
Solution Approach 2:
The patent applies local quality by making specific modifications at particular positions in the peptide sequence rather than changing the entire sequence. The core WYPGK sequence is maintained for memory improvement, while specific amino acids at defined positions can be modified to enhance antioxidant activity or stability, optimizing function without unnecessary synthesis complexity.
3Reliability
If the peptide is designed for high antioxidant activity, then oxidative stress-related memory impairments can be addressed, but the stability under acid-base and digestion conditions may be compromised
Solution Approach 1:
The patent uses parameter changes by selecting specific amino acid compositions and sequences that simultaneously provide high antioxidant activity and resistance to acid-base and enzymatic degradation. The modified amino acid sequences are chosen based on their chemical properties that confer both biological activity and stability under various conditions.
Solution Approach 2:
The patent creates composite peptide structures that combine amino acid residues with complementary properties - some positions provide antioxidant activity while others provide stability against acid-base and enzymatic degradation. This composite approach allows the peptide to fulfill multiple functional requirements simultaneously.
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
These derivative peptides significantly improve learning and memory in scopolamine-induced model mice, demonstrate high antioxidant capacity, and show stability under various pH and digestion conditions, making them suitable for use in medicaments and health care products.
Implementation Method 1
combined with the optimization and screening of antioxidant-related mitochondrial deacetylase SIRT3, a high-activity memory-improving derivative peptide is finally obtained
Implementation Method 2
The development of derivative peptides is one of the effective strategies to solve the problems that restrict the development and application of active peptides
Data Source
AI summary
The present disclosure provides a high-activity memory-improving derivative peptide and use thereof in preparation of memory-improving medicaments, health care products or foods, and belongs to the field of biotechnology. According to the present disclosure, proline 3 (Pro3) of a pine nut high-activity memory-improving peptide, WYPGK, is completely substituted with common amino acids to obtain 19 derivative peptides, and the derivative peptides are subjected to molecular docking with mitochondrial deacetylase sirtuin 3 and are screened by binding energy to obtain derivative peptides WYEGK, WYKGK, WYSGK, and WYFGK; solid-phase chemical synthesis is conducted by a peptide synthesizer; the derivative peptides are purified by reversed phase high performance liquid chromatography (RP-HPLC) and prepared by electrospray ionization mass spectrometry (ESI-MS). Morris water maze for scopolamine-induced memory impairment model mice demonstrates that the derivative peptides have high memory-improving activity.