Selective ETBR Polypeptides With Extended Half-Life for Stroke Recovery
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Solution Overview
Problem
Current ETBR agonists like IRL-1620 have a very short half-life and low exposure, requiring repeated administrations, which limits their efficacy and patient compliance in treating ETBR receptor-related diseases such as ischemic stroke.
Innovation Solution
Development of highly selective ETBR agonist polypeptides with prolonged half-lives through structure-activity relationship studies and structural modifications, reducing the frequency of administration and increasing in vivo exposure.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If IRL-1620 is used as an ETBR agonist, then the therapeutic effect is achieved, but the half-life is very short and exposure is very low
Solution Approach 1:
The patent modifies the chemical structure of IRL-1620 by changing specific parameters such as replacing certain amino acid residues with D-amino acid isomers and modifying the peptide backbone structure. These parameter changes in the molecular structure result in prolonged half-life and increased in vivo exposure while maintaining ETBR agonist activity
Solution Approach 2:
The patent creates composite peptide structures by combining modified amino acid sequences with specific structural elements. The resulting composite polypeptide structure exhibits enhanced stability and prolonged duration of action compared to the original IRL-1620 molecule
2Reliability
If repeated administrations of IRL-1620 are performed, then the therapeutic effect is maintained, but patient compliance is greatly reduced
Solution Approach 1:
By modifying the pharmacokinetic parameters of the ETBR agonist through structural changes, the patent achieves sustained therapeutic effects with less frequent administration, thereby improving patient compliance without sacrificing therapeutic reliability
3Ease of operation
If the frequency of administration is reduced, then patient compliance is improved, but the in vivo exposure is reduced
Solution Approach 1:
The patent changes the molecular parameters of the ETBR agonist to achieve longer circulation time and sustained release properties. This allows the drug to maintain adequate in vivo exposure levels even with reduced administration frequency, thus improving patient compliance
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
The polypeptides demonstrate lower side effects and a larger therapeutic window, effectively promoting the rehabilitation of stroke patients at the recovery stage with improved recovery outcomes.
Implementation Method 1
Endothelins exert their biological effects mainly by binding to an endothelin receptor (ETR) on the membrane of a target cell
Data Source
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AI summary
The present invention belongs to the field of biotechnology. Provided is a polypeptide and the use thereof. The polypeptide is established on the basis of a mechanism study on an ETBR agonist, and belongs to a highly selective agonist of ETBR. The polypeptide prolongs the half-life of a drug, increases in vivo exposure, and reduces the frequency of administration by means of study on structure-activity relationship and structural modification, and has a lower side effect than that of IRL-1620 in animal experiments, and a larger safety window of a drug. The polypeptide can be used for treating diseases related to an ETBR receptor, such as rehabilitation treatment of a patient with ischemic stroke in the acute stage and the recovery stage, so as to promote better recovery of the patient with stroke.