Multi-disulfide-bond Peptide ABPPk2 for Neuroprotection
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Solution Overview
Problem
Current treatments for stroke, particularly ischemic strokes, lack effective neuroprotective agents that can prevent neuronal damage and promote nerve function recovery.
Innovation Solution
Development of a multi-disulfide-bond long-chain peptide derived from Achyranthes bidentata Blume, specifically ABPPk2, which is characterized by its amino acid sequence, disulfide bond connection mode, and three-dimensional spatial structure, and is designed to interact with NMDA2B receptors for neuroprotection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current stroke treatment drugs (e.g., alteplase) are used for revascularization, then blood flow restoration is achieved, but neuroprotective effect is insufficient as the penumbra region cannot be converted into functional tissue
Solution Approach 1:
The patent uses a peptide molecule as an intermediary substance that mediates between the ischemic environment and neuronal cells. The peptide structure with specific amino acid sequences and disulfide bonds acts as a protective mediator that interferes with the pathological cascade, preventing excitotoxicity and promoting neuronal survival without requiring direct revascularization
Solution Approach 2:
The patent converts the harmful effects of ischemia into beneficial neuroprotective outcomes. By exposing neurons to controlled hypoxic-ischemic conditions in combination with the peptide treatment, the system triggers endogenous protective mechanisms and promotes neuronal resilience, transforming the damaging ischemic environment into a condition that stimulates neuroprotection and recovery
2Reliability
If NMDA receptor blockers are used to target glutamate-mediated excitotoxicity, then neuronal damage is reduced, but no effective neuroprotective agent has been clinically established yet
Solution Approach 1:
The patent employs specific parameter changes in the peptide structure, including the arrangement of cysteine residues to form disulfide bonds at specific positions, the sequence of amino acids, and the three-dimensional conformation. These parameter changes create a molecule with optimized neuroprotective activity that can be synthesized and produced clinically
Solution Approach 2:
The patent creates a composite peptide structure combining multiple functional elements: hydrophobic regions for membrane interaction, hydrophilic regions for solubility, disulfide bonds for structural stability, and specific amino acid sequences for receptor binding. This composite design integrates multiple protective mechanisms into a single therapeutic agent
3Object-generated harmful factors
If glutamate release mechanisms are activated during cerebral ischemia, then extracellular glutamate accumulates causing excitotoxicity, but no effective therapeutic drug can promote nerve function recovery
Solution Approach 1:
The patent applies preliminary anti-action by pre-treating neurons with the peptide before ischemic insult or at the onset of excitotoxicity. The peptide prepares the neuronal system by upregulating endogenous protective mechanisms, enhancing antioxidant defenses, and priming survival pathways, thereby preventing the full development of excitotoxic damage and facilitating subsequent recovery
Data Source
AI summary
A multi-disulfide-bond long-chain peptide with neuroprotective activity can reduce cellular calcium influx by inhibiting glutamate receptors to protect cortical neurons from excitotoxicity induced by glutamate. It can be an effective neuroprotective agent.