Modified aFGF Peptide Stability via N-Terminal Deletion
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Solution Overview
Problem
Native human acidic fibroblast growth factor (aFGF) peptides have stability issues due to their similarity with interleukin-1, leading to immuno-response activation and structural instability, which affects their therapeutic applications.
Innovation Solution
A modified peptide, aFGF135, is developed by deleting 20 amino acids from the N-terminal of native human aFGF and adding Alanine, resulting in a more stable sequence with improved thermal stability and distinct structural characterization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If native human aFGF is used, then biological activity is maintained, but stability is poor due to immuno-response activation and structural instability
Solution Approach 1:
The patent extracts and removes the problematic N-terminal 20 amino acids from native human aFGF that cause immuno-response activation and structural instability. This extraction eliminates the harmful similarity with interleukin-1 while preserving the core biological activity of the remaining 135 amino acids.
Solution Approach 2:
The patent modifies only the specific N-terminal region of the aFGF molecule where the problem originates, rather than changing the entire structure. The modification is localized to deleting residues 1-20 and adding Alanine at position 1, preserving the functional integrity of the C-terminal region while improving overall stability.
2Reliability
If N-terminal 20 amino acids are deleted and Alanine is added, then stability is improved, but sequence similarity with native aFGF is reduced
Solution Approach 1:
The patent changes the physical-chemical parameters of the N-terminal region by deleting 20 amino acids and adding a single Alanine residue. This parameter change fundamentally alters the thermal stability and immuno-genicity of the peptide while maintaining the core functional structure.
3Object-affected harmful factors
If native aFGF structure is preserved, then receptor binding capability is maintained, but resistance to denaturation and hydrolysis is insufficient
Solution Approach 1:
The patent applies preliminary anti-action by pre-modifying the N-terminal structure to prevent future denaturation and hydrolysis. The deletion of unstable N-terminal residues and addition of Alanine creates a more resistant structure that proactively defends against thermal and enzymatic degradation before damage occurs.
Data Source
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AI summary
An modified peptide of human acidic fibroblast growth factor (aFGF), comprising a native human aFGF shortened by a deletion of a deletion of 20 amino acids from N-terminal of the native human aFGF, and an addition of Alanine (Ala) before the shortened native aFGF is provided.