FGFR-Targeting Antagonistic Short Peptide P48 Stability
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Solution Overview
Problem
Current research on FGFR antagonistic peptides is hindered by issues related to easy degradation and short half-life, limiting their effectiveness as cancer treatments.
Innovation Solution
Development of a stable FGFR-targeting antagonistic short peptide, P48, with the amino acid sequence Ser-Pro-Pro-Arg-Tyr-Pro-Gly-Gly-Gly-Ser-NH2, which effectively binds to the extramembrane immunoglobulin domain of FGFR1, FGFR2, and FGFR3, exhibiting a prolonged half-life and strong anti-tumor activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If peptide inhibitors are used to target FGFR, then affinity and specificity are improved, but degradation resistance and half-life are worsened
Solution Approach 1:
The patent combines peptide inhibitors with cyclic peptides to create a composite structure. The cyclic peptide portion provides structural stability and degradation resistance, while the peptide inhibitor portion maintains high affinity and specificity for FGFR binding. This composite approach resolves the contradiction by integrating the advantages of both components.
Solution Approach 2:
The patent modifies the chemical structure parameters of the peptide inhibitor by incorporating cyclic peptide motifs and specific amino acid sequences (e.g., Ser-Pro-Pro-Arg-Tyr-Pro-Gly-Gly-Gly-Ser-NH2). These structural parameter changes enhance the peptide's resistance to degradation while preserving its binding affinity to FGFR.
2Ease of operation
If peptide inhibitors are used to target FGFR, then tissue penetration activity is improved, but half-life is worsened
Solution Approach 1:
The composite structure of peptide inhibitor combined with cyclic peptide maintains low molecular weight for excellent tissue penetration while the cyclic portion extends half-life through enhanced stability against proteolytic degradation.
Solution Approach 2:
The patent applies different structural characteristics to different portions of the molecule: the peptide inhibitor portion maintains properties for high tissue penetration, while the cyclic peptide portion provides properties for extended half-life and stability.
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 peptide P48 demonstrates significant specificity and stability, effectively inhibiting FGFR pathways, showing promise as a candidate drug for cancer treatment by inhibiting tumor cell growth and invasion both in vitro and in vivo.
Implementation Method 1
capable of targeting and binding to an extramembrane immunoglobulin domain of the FGFR
Data Source
AI summary
The present disclosure discloses a fibroblast growth factor receptor (FGFR)-targeting antagonistic short peptide, namely a short peptide compound P48 with the amino acid sequence of Ser-Pro-Pro-Arg-Tyr-Pro-Gly-Gly-Gly-Ser-NH2, where the short peptide compound P48 inhibits an FGFR pathway to inhibit cell proliferation and migration.