Fibronectin-Binding Peptide Sequence for Stable Tumor Targeting
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Solution Overview
Problem
Existing fibronectin-binding peptides suffer from poor stability in blood plasma, leading to a short half-life and reduced therapeutic or diagnostic efficacy, and they often have suboptimal biodistribution in tissues like tumors and organs such as the spleen and liver.
Innovation Solution
Development of a novel fibronectin-binding peptide, FnBPA5.1, with specific amino acid substitutions and deletions, which exhibits improved affinity for fibronectin and enhanced tumor uptake while reducing uptake in non-target organs like the spleen and liver.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing fibronectin-binding peptides are used, then they can bind to fibronectin, but they exhibit poor stability in blood plasma leading to short half-life
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence of the fibronectin-binding peptide (changing from natural peptide sequence to optimized synthetic sequence with specific substitutions), which improves both plasma stability and binding affinity simultaneously. The optimized sequence incorporates D-amino acids and specific structural modifications that resist proteolytic degradation while maintaining or enhancing fibronectin binding.
2Quantity of substance
If existing fibronectin-binding peptides are used, then they can reach target tissues, but they show suboptimal biodistribution in tumors and non-target organs
Solution Approach 1:
The patent applies local quality by optimizing specific regions of the peptide molecule differently - the N-terminal region is designed for plasma stability with protease resistance, while the fibronectin-binding region is optimized for high affinity and selective tumor targeting. This regional optimization enables differential properties within the same molecule, improving tumor uptake while reducing off-target accumulation in organs like spleen and liver.
3Device complexity
If existing fibronectin-binding peptides are used, then they have simple structure, but they exhibit reduced therapeutic or diagnostic efficacy
Solution Approach 1:
The patent applies composite materials by creating a hybrid peptide structure that combines multiple functional elements: D-amino acid residues for protease resistance, specific amino acid substitutions for enhanced fibronectin affinity, and optimized hydrophobicity/hydrophilicity balance for improved biodistribution. This composite approach integrates multiple properties into a single peptide molecule, achieving high efficacy without requiring complex multi-component systems.
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
FnBPA5.1 demonstrates tighter binding to fibronectin with a KD of 5.0 nM or less, increased tumor uptake, and reduced accumulation in non-target organs, thereby improving therapeutic and diagnostic efficacy.
Implementation Method 1
FnBPA5.1 demonstrates tighter binding to fibronectin with a KD of 5.0 nM or less
Data Source
AI summary
The present invention relates to fibronectin-binding peptides according to the sequenceFnI5BS-L1-FnI4BS-L2-FnI3BS-L3-FnI2BSwhich are useful in tumor or fibrosis diagnosis and therapy. Instant peptides show improved fibronectin-binding and biodistribution properties compared to the prior art. Furthermore, instant peptides may be conjugated to a payload and are useful in the treatment and/or prevention of diseases associated with pathological fibronectin accumulation, including cancer and fibrosis. Instant peptides are also useful in diagnosis of diseases associated with pathological fibronectin accumulation, including cancer and fibrosis.