Peptide Complex for CCK-B Receptor Targeting
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Solution Overview
Problem
Existing peptide drugs targeting cholecystokinin B receptors for cancer imaging and treatment face challenges such as high non-specific binding in the kidney, susceptibility to hydrolysis, and oxidation of methionine residues during radiolabeling, which hinders effective tumor visualization and treatment.
Innovation Solution
A novel complex comprising a synthetic peptide with the amino acid sequence Ala-Tyr-Gly-Trp-Nle-Asp-Phe, coupled with a metal chelator like DOTA, a glutamic acid peptide chain, and an albumin affinity ligand, specifically designed to target cholecystokinin B receptors, reduce non-specific binding, and enhance radioactive nuclide interaction with tumor cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If gastrin peptide drug is used to target cholecystokinin B receptors, then tumor targeting capability is improved, but non-specific binding in kidney increases
Solution Approach 1:
The patent modifies the peptide sequence parameters by replacing methionine residues with other amino acids and adjusting the peptide structure to change its binding characteristics. This results in reduced kidney binding while maintaining tumor targeting capability, as demonstrated by the improved biodistribution profiles in the patent data.
Solution Approach 2:
The patent creates a composite molecule by conjugating the peptide with a metal chelator (such as DOTA) and radioactive nuclide. This composite structure allows the peptide to maintain its tumor targeting function while the chelator-radiometal component provides therapeutic effect and enables imaging, while the modified peptide structure reduces kidney binding.
2Object-affected harmful factors
If sCCK8 peptide drug is used to target cholecystokinin B receivers, then kidney binding is reduced, but susceptibility to hydrolysis and oxidation increases
Solution Approach 1:
The patent changes the chemical composition parameters of the peptide by removing methionine residues (which are susceptible to oxidation) and sulfated tyrosine residues (which are easily hydrolyzed). The modified peptide sequence maintains low kidney binding while significantly improving stability against hydrolysis and oxidation.
Solution Approach 2:
The patent uses a peptide design that prioritizes stability and longevity in the bloodstream. By eliminating labile residues, the peptide achieves extended circulation time and improved reliability, effectively replacing the need for rapid action with sustained activity.
3Adaptability or versatility
If methionine residues are included in the peptide sequence, then peptide functionality is maintained, but oxidation during radiolabeling occurs
Solution Approach 1:
The patent extracts and removes the problematic methionine residues from the peptide sequence before radiolabeling. This elimination prevents oxidation during the labeling process while the remaining peptide structure maintains all necessary functions for cholecystokinin B receptor binding and tumor targeting.
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 complex achieves specific binding to cholecystokinin B receptors, reducing non-specific binding and radiation exposure to normal organs, thereby enhancing the therapeutic effect and tumor visualization, as demonstrated by improved imaging and tumor growth inhibition results.
Implementation Method 1
The complex includes a synthetic peptide, a metal chelator, a peptide chain and an albumin affinity ligand. The metal chelator is coupled with the synthetic peptide
Implementation Method 2
The complex achieves specific binding to cholecystokinin B receptors, reducing non-specific binding and radiation exposure to normal organs
Implementation Method 3
the radioactive nuclide is selected from the group consisting of gallium-66 (Ga-66), gallium-67 (Ga-67), gallium-68 (Ga-68), zirconium-89 (Zr-89), lutetium-177 (Lu-177), indium-111 (In-111), and iodine-123 (I-123)
Data Source
AI summary
Disclosed herein is a drug complex having a synthetic peptide, which has an amino acid sequence of SEQ ID: NO.1; a metal chelator coupled to the synthetic peptide; and a peptide chain disposed between the synthetic peptide and the metal chelator, wherein the peptide chain is composed of plural glutamate molecules.