Tissue Protective Peptides Resolving EPO Side Effects
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Solution Overview
Problem
Current treatments for tissue protection, particularly in conditions like anemia and tissue damage, rely on erythropoietin (EPO) but lack effective peptides that mimic its tissue-protective properties without erythropoietic activity, and existing peptides may not adequately address neural and excitable tissue protection.
Innovation Solution
Development of isolated polypeptides with specific amino acid sequences, such as WEHVNAIQEARRLL, that mimic the spatial localization of key residues from EPO, designed to bind to a tissue protective receptor complex, offering cellular protection without erythropoietic activity and capable of traversing endothelial cell barriers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If erythropoietin (EPO) is used for tissue protection, then tissue protective activity is improved, but erythropoietic activity is unintended and may cause unwanted effects
Solution Approach 1:
The patent segments the EPO protein into distinct functional domains: a receptor binding domain (residues 1-23) and a tissue protective domain (residues 24-165). By isolating and using only the tissue protective domain ( peptides of 1-30 amino acids), the invention achieves tissue protection without the erythropoietic effects of full-length EPO, thus resolving the contradiction between desired tissue protection and unwanted erythropoietic effects.
Solution Approach 2:
The invention extracts the tissue protective function from the full EPO molecule by identifying and isolating specific peptide sequences (residues 24-165) that mediate tissue protection independently of erythropoietic activity. This extraction allows the use of short peptides (1-30 amino acids) that provide tissue protection without causing unwanted erythropoietic effects.
2Reliability
If full-length EPO is used, then tissue protection is achieved, but the peptide size and complexity increase
Solution Approach 1:
The patent divides the 165-amino acid EPO protein into functional segments, focusing on the tissue protective domain (residues 24-165) which can be represented as short peptides of 1-30 amino acids. This segmentation reduces the peptide size from full-length EPO (165 amino acids) to much shorter sequences while maintaining tissue protective activity, thus resolving the contradiction between effectiveness and complexity.
Solution Approach 2:
The invention extracts and isolates the minimal peptide sequences (1-30 amino acids) from full-length EPO that are sufficient to mediate tissue protection. By taking out only the essential tissue protective domain and removing the erythropoietic domain, the invention achieves the same tissue protection with significantly reduced peptide size and structural complexity.
3Reliability
If existing peptides are used for tissue protection, then some protective activity is achieved, but neural and excitable tissue protection is insufficient
Solution Approach 1:
The patent identifies specific local regions within the EPO tissue protective domain that are critical for neural and excitable tissue protection. By focusing on these specific local sequences (such as residues 58-82 and other conserved regions), the invention enhances the peptide's ability to protect neural tissues while maintaining general tissue protective activity, thus resolving the contradiction between general protection and specific neural protection.
Solution Approach 2:
The invention modifies peptide parameters by selecting and optimizing specific amino acid sequences, lengths, and structural features within the tissue protective domain. By changing these parameters (such as focusing on conserved residues and specific structural motifs), the peptide achieves enhanced activity against neural and excitable tissues while maintaining general tissue protective properties.
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
These polypeptides demonstrate cellular protective activity in both in vivo and in vitro models, particularly in neural tissues, providing neuroprotection and enhancing tissue viability, while lacking erythropoietic effects, thus offering a targeted therapeutic approach for tissue injuries and disorders.
Implementation Method 1
The tissue protective peptides of the invention may bind to a tissue protective receptor complex
Data Source
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AI summary
The present invention is directed to novel tissue protective peptides. The tissue protective peptides of the invention may bind to a tissue protective receptor complex. In particular, the present invention is drawn to tissue protective peptides derived from or sharing consensus sequences with portions of cytokine receptor ligands, including Erythropoietin (EPO), that are not involved in the binding of the ligand to the receptor complex, e.g., to the EPO receptor homodimer. Accordingly, the tissue protective peptides of the invention are derived from the amino acid sequences of regions of cytokine receptor ligands that are generally located on or within the region of the ligand protein that is opposite of the receptor complex, i.e., are generally derived from amino acid sequences of regions of the ligand protein that face away from the receptor complex while the ligand is bound to the receptor. The invention is further directed to the consensus sequences for use in engineering a synthetic tissue protective peptide. These tissue protective peptides also include fragments, chimeras, as well as peptides designed to mimic the spatial localization of key amino acid residues within the tissue protective receptor ligands, e.g., EPO. The invention further encompasses methods for treating or preventing a disease or disorder using tissue protective peptides of the current invention. The invention also encompasses methods for enhancing excitable tissue function using tissue protective peptides of the current invention.