VEGF Receptor Binding Peptides for Angiogenesis Control
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Solution Overview
Problem
Current therapies lack effective compounds to modulate VEGF-dependent biological responses, particularly in treating angiogenesis-related diseases and imaging angiogenic vasculature, as existing agents often have limited specificity and efficacy in targeting VEGF receptors.
Innovation Solution
Development of synthetic peptides mimicking the β-hairpin region 79-92 of VEGF or PlGF to bind to VEGF receptors, which can promote or inhibit angiogenesis, serving as therapeutic, diagnostic, and imaging agents for pathologies involving VEGF receptor overexpression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing agents are used to target VEGF receptors, then therapeutic intervention is provided, but specificity and efficacy are limited
Solution Approach 1:
The patent creates simplified peptide copies (compounds of formula I) that mimic the critical β-hairpin region 79-92 of VEGF or PlGF. These peptide copies replicate the receptor-binding functionality of the full-length growth factors while being structurally simpler and more controllable therapeutically
Solution Approach 2:
The invention extracts and isolates the essential functional region (β-hairpin region 79-92) from the complete VEGF or PlGF protein structure. By focusing only on this critical binding domain, the patent creates minimal sufficient structures that achieve therapeutic effect without the complexity of the full protein
2Measurement precision
If synthetic peptides mimicking VEGF β-hairpin region are developed, then specificity and efficacy in binding VEGF receptors is improved, but manufacturing complexity increases
Solution Approach 1:
The patent systematically varies parameters within the peptide structure (amino acid substitutions at positions X1-X10, different Y residues at positions Y1-Y7) to optimize binding specificity while maintaining synthetic feasibility. This parameter optimization allows balancing specificity gains with manufacturing considerations
3Reliability
If peptides are designed to mimic VEGF region 79-92, then pro- or anti-angiogenic activity is achieved, but structural stability challenges arise
Solution Approach 1:
The patent employs composite peptide structures combining natural amino acids with unnatural amino acids (X1-X10 positions) to enhance structural stability. The disulfide bridge between Cys residues and the specific amino acid composition create a stable composite structure that maintains the β-hairpin conformation necessary for biological activity
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 peptides effectively bind to VEGF receptors, demonstrating pro- or anti-angiogenic activity, enabling targeted therapy and imaging of angiogenic processes, particularly in cancer and other angiogenesis-dependent pathologies, with potential applications in treating various diseases and diagnosing conditions related to VEGF receptor overexpression.
Implementation Method 1
These compounds mimic the β-hairpin region 79-92 of VEGF (or the corresponding fragment of Placenta Growth Factor) which is involved in receptors recognition
Data Source
AI summary
Compounds of general formula (1): X1Y1X2Y2X3Y3X4Y4Y5X5X6Y6X7Y7X8X9X10 wherein X1-X10 are any natural or unnatural amino acids and Y1 is Gln; Y2 is Met or Leu; Y3 is He; Y4 is Pro or Ser; Y5 is His or Gly; Y6 is Gln or Pro; Y7 is He or Tyr or their homolog or ortolog are described; these compounds are able to bind to the VEGF receptors and to modulate the angiogenesis mediated by the VEG.