Fragmented CRS Peptide Monomer Stability via Cysteine Substitution
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Solution Overview
Problem
Existing fragmented cysteineyl-tRNA synthetase (CRS) peptides face challenges in development as drugs due to degradation issues when affinity tags are removed and difficulty in maintaining their form as monomers, which affects their anticancer and immune-enhancing activities.
Innovation Solution
A novel fragmented CRS peptide with the amino acid sequence of SEQ ID NO: 2 or sequences showing 95% homology, which maintains its form as a monomer without degradation, and is used in vaccine adjuvants and cancer treatment compositions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If affinity tags are attached to CRS fragment peptide, then the peptide can be purified and produced, but the peptide degrades when affinity tags are removed
Solution Approach 1:
The patent extracts and removes the affinity tags (such as His-tag, GST-tag, or FLAG-tag) from the CRS fragment peptide after purification. The peptide is produced with the affinity tag for easy purification, then the tag is cleaved off to obtain the stable, active peptide without the tag that causes degradation.
Solution Approach 2:
The affinity tag is attached preliminarily during peptide production to facilitate purification, then removed before the peptide is used. This preliminary attachment allows for easy manufacturing while ensuring the final stable peptide product is tag-free.
2Reliability
If CRS fragment peptide is used in conventional form, then it shows anticancer activity, but it cannot maintain monomer form and forms multimers
Solution Approach 1:
The patent modifies specific local regions of the CRS fragment peptide by substituting certain amino acids (such as replacing cysteine residues with serine or alanine at specific positions) to prevent unwanted multimerization while preserving the local structure necessary for anticancer activity. This local modification maintains the monomer form without sacrificing therapeutic function.
Data Source
AI summary
The present invention relates to a novel fragmented CRS peptide exhibiting immune enhancement activity, and a use thereof, and, more specifically, to a novel peptide consisting of an amino acid sequence of SEQ ID NO: 2, and a use thereof as a vaccine adjuvant and a cancer therapeutic agent. A peptide disclosed in the present invention is a CRS fragment disclosed for the first time in the present specification and exhibits an anti-cancer activity and immune enhancement activity.