TAFA-4 Mature Peptide Segmentation for Pain Relief
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Solution Overview
Problem
Current treatments for chronic pain, such as non-steroidal anti-inflammatory agents (NSAIDs) and opioids, have limited efficacy and are associated with adverse effects, highlighting the need for alternative therapeutic agents that can be manufactured on an industrial scale and in a cost-effective way.
Innovation Solution
The development of a novel peptide, TT1, and its variants, such as TT6, derived from a specific fragment of the human TAFA-4 protein, which exhibit antalgic or analgesic activity, are easy to produce, and are highly efficacious against acute, subacute, or chronic pain.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If full-length TAFA-4 protein is produced by chemical synthesis, then the therapeutic activity is maintained, but the manufacturing complexity and cost increase due to requiring assembly of at least 4 peptide segments and 3 ligation purification steps
Solution Approach 1:
The full-length TAFA-4 protein sequence is divided into a signal peptide region (amino acids 1-42) and a mature peptide region (amino acids 43-140). By eliminating the signal peptide and only synthesizing the mature region, the number of synthesis segments is reduced from at least 4 segments to a single continuous peptide sequence, eliminating the need for multiple ligation steps while maintaining therapeutic activity.
Solution Approach 2:
The signal peptide region (amino acids 1-42) is extracted and removed from the full-length TAFA-4 protein sequence. This extracted portion is non-essential for the therapeutic analgesic activity, allowing the mature peptide (amino acids 43-140) to be produced independently as a standalone therapeutic agent with simplified manufacturing.
2Reliability
If recombinant TAFA-4 protein is produced, then the therapeutic activity is achieved, but the yield is limited due to refolding challenges and improper disulfide bridging patterns
Solution Approach 1:
The signal peptide region is extracted and removed, and the mature peptide is produced as a separate entity. This extraction allows the mature peptide to be synthesized or expressed without the complicating factors of signal peptide processing and refolding, thereby improving production yield while maintaining therapeutic activity.
3Manufacturing precision
If multiple purification steps are performed to obtain high purity recombinant TAFA-4, then the protein quality is improved, but the production time and cost increase
Solution Approach 1:
By extracting and removing the signal peptide region, the mature peptide can be produced as a defined, discrete sequence that is simpler to purify. This extraction reduces the complexity of purification requirements compared to full-length protein production, thereby reducing production time while maintaining high purity standards.
4Reliability
If chemical synthesis of full-length TAFA-4 is performed, then the therapeutic activity is maintained, but the manufacturing cost increases due to low yields from multiple ligation steps
Solution Approach 1:
The protein is segmented into signal peptide (removed) and mature peptide (retained). This segmentation strategy eliminates the need for multiple ligation steps required for full-length protein synthesis, thereby reducing manufacturing complexity and cost while maintaining the therapeutic activity of the mature peptide region.
Solution Approach 2:
The signal peptide is extracted and removed from the synthesis plan. This extraction allows the mature peptide to be synthesized as a single continuous sequence rather than requiring assembly of multiple segments, dramatically reducing the number of purification steps and associated costs while preserving therapeutic efficacy.
Data Source
AI summary
The present invention relates to novel peptides, compositions and kits comprising the peptides, for use as active ingredient for preventing or treating pain in a subject in need thereof. Also herein described is an in vitro or ex vivo method for modulating the expression of these peptides.