Cyclopeptide Derivatives for CXCR4 Imaging and Therapy
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Solution Overview
Problem
Current CXCR4 ligands often lose affinity to the CXCR4 receptor when additional moieties are attached for imaging or therapeutic applications, necessitating the development of new ligands with high affinity that can incorporate functional moieties without compromising binding capabilities.
Innovation Solution
The development of cyclopeptide derivatives with a specific linker and additional moieties, such as a detectable label, which maintain high affinity to the CXCR4 receptor, enabling various imaging and therapeutic applications, including endoradiotherapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If additional moieties are attached to CXCR4 ligands for imaging or therapeutic applications, then the functionality for imaging and therapy is improved, but the affinity to the CXCR4 receptor deteriorates
Solution Approach 1:
The CXCR4 ligand is divided into distinct functional segments: the core cyclic pentapeptide structure (maintaining receptor affinity) and separate additional moieties (providing imaging/therapeutic functionality) connected via linkers. This segmentation allows each component to perform its specific function independently, resolving the contradiction between maintaining affinity and adding functionality.
Solution Approach 2:
Linker structures serve as intermediaries between the core CXCR4 ligand and additional functional moieties. These linkers mediate the connection in a way that preserves the ligand-receptor interaction while enabling the attached functional groups to perform imaging or therapeutic actions without interfering with binding affinity.
2Adaptability or versatility
If the structure of CXCR4 ligands is modified to incorporate functional moieties, then the application versatility is improved, but the binding capacity deteriorates
Solution Approach 1:
The cyclic pentapeptide core structure is preserved with high structural integrity to maintain binding capacity, while modifications are localized to specific positions on the ligand where linkers and functional moieties are attached. This local modification approach ensures that the critical binding region remains unchanged while gaining functional versatility.
Solution Approach 2:
The core cyclic pentapeptide structure serves as a universal platform that can accommodate multiple different functional moieties (imaging agents, therapeutic groups) through standardized linker attachment points. This universal core structure maintains consistent binding capacity across various functional configurations.
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
These compounds demonstrate high affinity to the CXCR4 receptor even with attached linker and additional moieties, making them suitable for medical applications like imaging and therapeutic uses, such as endoradiotherapy, while retaining sufficient binding capacity.
Implementation Method 1
The compounds of the invention are believed to be capable of binding to the seven transmembrane G-protein coupled chemokine receptor CXCR4 with high affinity and are thus considered CXCR4 ligands.
Data Source
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AI summary
The present invention, among others, relates to a compound having a structure according to formula (I) or a pharmaceutically acceptable salt thereof, wherein Xaa1 to Xaa4 are independently of each other, an optionally N-alkylated natural or unnatural amino acid, R is H or methyl, L is a linker moiety, Ar is a spacer comprising an aromatic moiety, and D comprises, preferably is i) a combination of an organic complexation agent and a detectable label; or ii) a detectable label, an organic complexation agent or an active substance, said active substance particularly being selected from cytotoxic agents, lipids, sugars, sugar conjugates, sugar derivatives, proteins and combinations thereof, with the proviso that -L-Ar-D does not comprise a 18F-benzoyl residue.