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 competitive receptor binding with other FGFs, 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 peptide with enhanced stability and a distinct structural characterization, as evidenced by its resistance to degradation at physiological temperatures and structural integrity at elevated temperatures.
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 competitive receptor binding
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 similarity with interleukin-1. This deletion eliminates the harmful factors while preserving the core biological activity of the peptide.
Solution Approach 2:
The patent modifies only the specific N-terminal region of the aFGF peptide where the problem originates (amino acids 1-20), while leaving the rest of the peptide structure intact. This localized modification approach maintains the functional domains while eliminating immunogenicity.
2Reliability
If native human aFGF is used, then therapeutic function is provided, but structural integrity is compromised at physiological and elevated temperatures
Solution Approach 1:
The patent changes the physical-chemical parameters of the peptide by deleting 20 amino acids and adding Alanine, which fundamentally alters the peptide's thermal stability profile. This parameter change enables the peptide to maintain structural integrity at both physiological and elevated temperatures.
Solution Approach 2:
The patent creates a modified version (aFGF135) that copies the essential functional structure of native aFGF while eliminating the unstable N-terminal region. The modified peptide serves as a stable replica that maintains therapeutic function with improved thermal resistance.
3Duration of action of moving object
If native human aFGF is used, then biological activity is preserved, but degradation occurs at body temperature
Solution Approach 1:
The patent removes the degradation-prone N-terminal 20 amino acids from native aFGF, eliminating the portion of the molecule that is most susceptible to degradation at body temperature. This extraction extends the duration of action by preventing breakdown.
Solution Approach 2:
The patent performs preliminary modification by deleting the unstable N-terminal region and adding Alanine before the peptide is administered therapeutically. This preliminary structural optimization ensures long-term stability and extended duration of action in vivo.
Data Source
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.