Cyclic NGR Peptide Composition for Stable CD13 Tumor Targeting
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Solution Overview
Problem
Current cyclic peptides used for tumor radiotracers targeting NGR have susceptibility to biodegradation and chemical modification, limiting their biological stability and in vivo retention time, which affects their effectiveness in molecular imaging and targeted radionuclide therapy.
Innovation Solution
A new cyclic peptide with the sequence cyclo(X1X2X3X4X5X6) is developed, where X1 is asparagine, X2 is glycine or sarcosine, X3 is arginine, X4 is threonine or tyrosine, X5 is lysine, and X6 is tyrosine, with a method involving condensation reactions and solid-phase synthesis to enhance stability and affinity for CD13 receptors, allowing for radionuclide labeling and targeted tumor imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cyclic peptides (e.g., cyclo(CNGRC)) are used for tumor radiotracers, then they can bind to CD13 receptors on tumor blood vessels, but they are susceptible to biodegradation and chemical modification, resulting in poor biological stability and short in vivo retention time
Solution Approach 1:
The patent modifies the peptide sequence parameters by replacing specific amino acids (e.g., using N-methylated amino acids, D-amino acids, or non-natural amino acids) to enhance resistance against proteolytic degradation while maintaining CD13 binding affinity. This parameter change in amino acid composition directly improves biological stability and extends in vivo retention time
Solution Approach 2:
The patent creates composite peptide structures by combining multiple modified amino acid types (e.g., N-methylated amino acids combined with D-amino acids, or peptide sequences conjugated with stabilizing moieties) to achieve both high stability and prolonged circulation time in vivo
2Reliability
If polypeptides containing NGR structures are used to target tumor vascular tissues, then they can bind to CD13 receptor-positive blood vessels with high specificity, but their conformational flexibility reduces binding stability
Solution Approach 1:
The patent segments the flexible peptide chain by introducing rigidifying constraints such as cyclic structures, disulfide bonds, or rigid amino acid residues (e.g., proline, hydroxyproline) at specific positions. This segmentation maintains the essential conformational flexibility for CD13 binding while preventing excessive flexibility that reduces binding stability
Solution Approach 2:
The patent introduces curved or cyclic structural elements (e.g., cyclic peptides, beta-turns, or rigidified conformations) that constrain the peptide backbone into stable three-dimensional structures. This curvature reduces conformational entropy and enhances binding stability while preserving the spatial arrangement necessary for CD13 receptor recognition
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 new cyclic peptide exhibits higher in vivo stability, stronger affinity for CD13 receptors, and improved targeting ability, enabling accurate tumor molecular imaging and therapeutic radionuclide delivery for cancer detection and treatment.
Implementation Method 1
polypeptides containing NGR structures can bind to CD13 receptor-positive blood vessels in tumor tissues
Data Source
AI summary
Provided is a cyclic peptide, having a sequence of cyclo(X1X2X3X4X5X6), wherein X1 is asparagine; X2 is glycine or sarcosine; X3 is arginine; X4 is selected from a group consisting of threonine, tyrosine, and phenylalanine; X5 is lysine; and X6 is selected from a group consisting of tyrosine, valine, and glutamic acid. Provided is a method for preparing the cyclic peptide. Provided is a complex, comprising the cyclic peptide, a linker, and a chelating agent. Provided is a use of the complex as a radionuclide-labeled targeting molecule. Provided is a radionuclide labeling method, comprising contacting a complex that chelates a radionuclide with an object to be labeled by the radionuclide.