uPAR-Targeted Peptide Conjugates with Oligoethylene Glycol Linkers
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Solution Overview
Problem
Current uPAR-targeting peptide conjugates for cancer imaging and therapy lack enhanced binding affinity and solubility, leading to suboptimal tumor uptake and radiation dose delivery.
Innovation Solution
Incorporation of a linker group comprising oligoethylene glycols or other short oligomers, such as oligo-glycerol or oligo-lactic acid, connected by covalent bonds to amino acids, which enhances binding affinity and solubility, stabilizes the peptide-radionuclide complex, and increases tumor uptake and retention.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If conventional peptide conjugates are used for uPAR targeting, then the structure is simple, but binding affinity and tumor uptake are insufficient
Solution Approach 1:
The peptide conjugate is divided into distinct functional segments: a uPAR-binding peptide sequence (e.g., AE105), a linker group (e.g., oligoethylene glycol), and a radionuclide-chelator complex. This segmentation allows each component to optimize its function independently, with the linker providing solubility and spacing while the peptide maintains binding affinity.
Solution Approach 2:
The invention combines multiple chemical components into a composite conjugate structure: the peptide sequence DChaFsrYLWS (or variants), connected via a linker group comprising oligoethylene glycols or other short oligomers (oligo-glycerol, oligo-lactic acid, or carbohydrates), which is further connected to a radionuclide through a chelating agent. This composite structure integrates binding, solubility, and radiolabeling functions.
2Quantity of substance
If conventional peptide conjugates are used, then solubility is limited, but adding solubility-enhancing groups may reduce binding affinity
Solution Approach 1:
The linker group acts as an intermediary between the uPAR-binding peptide and the radionuclide-chelator complex. Specifically, oligoethylene glycol linkers or other short oligomers (oligo-glycerol, oligo-lactic acid, carbohydrates) provide hydrophilicity and solubility enhancement while maintaining adequate spacing and orientation to preserve peptide-receptor binding affinity.
3Productivity
If tumor uptake is increased, then radiation dose delivery improves, but retention time must be prolonged
Solution Approach 1:
The invention optimizes multiple parameters of the peptide conjugate: the peptide sequence (e.g., DChaFsrYLWS or variants like Asp-Cha-Phe-ser-arg-Tyr-Leu-Trp-Ser), the linker group composition (oligoethylene glycol units or alternative oligomers), and the radionuclide selection (e.g., 64Cu, 68Ga, 177Lu). These parameter changes collectively enhance both tumor uptake efficiency and retention duration, enabling improved radiation dose delivery to cancer tissues.
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 use of these linker groups in uPAR-targeting peptide conjugates results in improved binding properties, increased tumor uptake, and prolonged retention, potentially delivering a higher radiation dose to cancer tissues.
Implementation Method 1
suited for non-invasive PET imaging
Implementation Method 2
SPECT imaging or targeted radionuclide therapy
Implementation Method 3
targeted radionuclide therapy
Data Source
AI summary
The present invention describes Urokinase Plasminogen Activator Receptor (uPAR) targeted radiolabeled conjugates suited for non-invasive PET imaging, SPECT imaging or targeted radionuclide therapy. In particular, but not limited to, the invention related to imaging and therapy of cancer diseases.