Polypeptides Modulating Angiopoietin-Tie Interactions
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Solution Overview
Problem
Current therapies lack effective agents to modulate angiopoietin-Tie interactions, which are crucial in angiogenesis-related diseases such as cancer, diabetic retinopathy, and rheumatoid arthritis, as existing treatments have limitations in inhibiting excessive or inadequate blood vessel formation.
Innovation Solution
Development of amino acid sequences and polypeptides that specifically bind to Tie1, Tie2, Ang1, Ang2, Ang3, Ang4, Angptl1, Angptl2, Angptl3, Angptl4, and Angptl5 with high affinity, acting as agonists, antagonists, or inverse agonists to modulate angiopoietin-Tie interactions and signaling pathways.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If existing treatments are used to address angiogenesis-related diseases, then treatment options are limited, but the ability to effectively inhibit excessive or inadequate blood vessel formation is insufficient
Solution Approach 1:
The patent employs parameter changes by developing polypeptides with varying amino acid sequences that exhibit different binding affinities to angiopoietin-Tie complexes. By modifying sequence parameters and structural characteristics, the invention creates a range of agents with optimized effectiveness for inhibiting pathological angiogenesis while maintaining adaptability to different disease contexts.
Solution Approach 2:
The invention applies local quality by designing polypeptides with specific regional characteristics in their amino acid sequences that target particular epitopes or binding interfaces of the angiopoietin-Tie system. This localized optimization allows the agents to selectively modulate specific interactions within the broader angiogenesis pathway, enhancing therapeutic precision.
2Reliability
If amino acid sequences are designed to bind with high affinity to multiple angiopoietin-Tie components, then therapeutic effectiveness is improved, but sequence complexity and development difficulty increase
Solution Approach 1:
The patent implements universality by designing polypeptides capable of binding to multiple components within the angiopoietin-Tie system (including Tie1, Tie2, Ang1, Ang2, and related ligands) through a single molecular structure. This multi-functional approach allows one polypeptide sequence to effectively inhibit various pathological angiogenesis processes, improving therapeutic reliability without proportionally increasing complexity.
Solution Approach 2:
The invention applies segmentation by dividing the angiopoietin-Tie interaction interface into discrete binding regions that can be independently targeted by modular polypeptide segments. This segmentation strategy enables the construction of complex binding specificities through combinatorial assembly of simpler structural modules, managing sequence complexity while achieving high-affinity multi-target binding.
Data Source
AI summary
The present invention relates to amino acid sequences that are directed against proteins from the group of the Angiopoietin/Tie family such as Tie1, Tie2, Ang1, Ang2, Ang3, Ang4, Angptl1, Angptl2, Angptl3, Angptl4, Angptl5, Angptl6, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more of such amino acid sequences.