Conotoxin Peptide κ-CPTx-btl03 Calcium Channel Blockade
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Solution Overview
Problem
Current treatments for hypertension lack effective polypeptide calcium channel blockers with high selectivity and safety, necessitating the development of novel compounds that can inhibit calcium ion channels to manage cardiovascular diseases.
Innovation Solution
The development of a conotoxin peptide κ-CPTx-btl03, including its encoding polynucleotide, expression vector, and host cell, which is derived from Conus betulinus venom, and can be synthesized or extracted, to inhibit high-voltage activated calcium ion channels, similar to Nifedipine's efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If small molecule calcium channel blockers like nifedipine are used, then blood pressure can be reduced through calcium channel inhibition, but the drugs lack high selectivity and safety profiles
Solution Approach 1:
The patent changes the chemical nature of calcium channel blockers from small molecules to polypeptides, specifically designing a conotoxin-based peptide with 29 amino acids that selectively targets high-voltage activated calcium channels. This parameter change enables high selectivity and safety while maintaining efficacy in treating hypertension and cardiovascular diseases
Solution Approach 2:
The patent creates a composite peptide structure by combining multiple cysteine residues (6 cysteines forming 3 disulfide bonds) with specific amino acid sequences derived from Conus betulinus venom. This composite structure provides both stability and high selectivity for calcium channel blockade, resolving the contradiction between reliability and manufacturability
2Reliability
If polypeptide calcium channel blockers are developed, then high selectivity and safety can be achieved, but fewer such drugs have been successfully developed compared to small molecule blockers
Solution Approach 1:
The patent extracts the active calcium channel blocking component from Conus betulinus venom and isolates the specific conotoxin peptide sequence. By taking out only the essential 29-amino-acid sequence with six cysteines, the patent creates a simplified yet highly effective polypeptide blocker that overcomes the historical difficulties in developing polypeptide-based calcium channel blockers
Solution Approach 2:
The patent segments the complex venom mixture into a specific functional unit - the 29-amino-acid conotoxin peptide with defined disulfide bond structure. This segmentation allows for precise characterization, reproduction, and clinical development, thereby improving the productivity and success rate of polypeptide calcium channel blocker development
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
κ-CPTx-btl03 effectively suppresses high-voltage activated calcium ion channels, demonstrating comparable inhibitory activity to Nifedipine, offering a promising treatment for hypertension, angina pectoris, and coronary heart disease with high selectivity and safety.
Implementation Method 1
κ-CPTx-btl03 effectively suppresses high-voltage activated calcium ion channels, demonstrating comparable inhibitory activity to Nifedipine
Data Source
AI summary
Provided are a conotoxin peptide κ-CPTx-bt103 and a derivative polypeptide. The amino acid sequence of the conotoxin peptide is indicated by SEQ ID NO: 1. Also provided are a conotoxin peptide preparation method and uses of the conotoxin peptide in the treatment of diseases related to a calcium ion channel.