RANKL DE Loop Oligopeptide Inhibiting Cytokine Secretion
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Solution Overview
Problem
Current therapeutic agents for infarction diseases, such as thrombolytic agents and edaravone, have limitations in timing and efficacy, particularly in treating infarction diseases when administered several hours after ischemic area formation, and they do not effectively inhibit proinflammatory cytokine secretion.
Innovation Solution
An oligopeptide containing a DE loop sequence of the RANKL protein with specific β-strand sequences, which inhibits proinflammatory cytokine secretion from cells, providing therapeutic effects even when administered several hours after ischemic area formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If thrombolytic agents are used to treat infarction diseases, then therapeutic effectiveness is improved, but the administration time window is limited to within 4.5 hours after ischemic area formation
Solution Approach 1:
The invention extracts the critical functional region (DE loop sequence) from the full-length RANKL protein to create a minimized oligopeptide (15-50 amino acids) that retains proinflammatory cytokine inhibition activity. This extracted region can be administered effectively beyond the 4.5-hour window of thrombolytic agents, solving the time window limitation while maintaining therapeutic effectiveness.
Solution Approach 2:
The invention changes the molecular size parameter from full-length RANKL protein to a minimized oligopeptide fragment (15-50 amino acids). This parameter change enables the therapeutic agent to maintain activity at later time points after ischemic injury, extending the effective administration window beyond what is possible with conventional thrombolytic agents.
2Reliability
If edaravone is administered to treat infarction diseases, then neuroprotection is achieved, but multiple administrations (twice daily) are required
Solution Approach 1:
The invention extracts the essential functional domain (DE loop sequence with β-strand D) from full-length RANKL to create a minimized oligopeptide that achieves neuroprotection with single administration. This extracted region provides sustained activity that eliminates the need for multiple daily doses required by edaravone, improving treatment productivity while maintaining neuroprotective efficacy.
3Reliability
If full-length RANKL protein is used to inhibit proinflammatory cytokines, then therapeutic effects are achieved, but stability and economical efficiency are reduced
Solution Approach 1:
The invention extracts only the essential DE loop sequence (amino acids 116-140) and β-strand D region from full-length RANKL protein to create a stable minimized oligopeptide (15-50 amino acids). This extracted fragment maintains proinflammatory cytokine inhibition activity while significantly improving compositional stability and economical efficiency compared to the full-length protein.
Solution Approach 2:
The invention segments the full-length RANKL protein into distinct functional regions, identifying and isolating the critical DE loop sequence and β-strand D region. This segmentation approach creates a minimized oligopeptide that retains therapeutic activity while improving stability and reducing production costs compared to using the complete protein.
4Reliability
If full-length RANKL protein is used for therapy, then proinflammatory cytokine inhibition is achieved, but production cost and complexity increase
Solution Approach 1:
The invention extracts the minimal functional sequence (DE loop + β-strand D, 15-50 amino acids) from full-length RANKL protein. This extracted oligopeptide maintains cytokine inhibition activity while dramatically simplifying production processes and reducing manufacturing costs, making the therapy more economically viable compared to producing full-length protein.
Solution Approach 2:
The invention segments RANKL protein to identify and produce only the essential therapeutic region (DE loop sequence with β-strand D). This segmentation enables simplified synthesis and manufacturing of the minimized oligopeptide, improving ease of manufacture and production efficiency while maintaining the required biological activity.
Data Source
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AI summary
Provided is an oligopeptide having preventive and therapeutic effects on infarction diseases. The oligopeptide contains a DE loop sequence of RANKL protein, and has inhibitory activity on proinflammatory cytokine secretion from cells.