Cyclic Peptide Structure for Stable CD13 Radionuclide 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 tumor imaging and 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, X5 is lysine, and X6 is tyrosine, coupled with a linker and chelating agent for radionuclide labeling, enhancing stability and affinity for CD13 receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cyclic peptides are used for tumor radiotracers, then they can target CD13 receptors, but they are susceptible to biodegradation and chemical modification
Solution Approach 1:
The patent modifies the chemical structure of cyclic peptides by changing amino acid sequences, introducing non-standard amino acids, and adjusting cyclization patterns to reduce susceptibility to biodegradation and chemical modification while maintaining CD13 receptor targeting capability
Solution Approach 2:
The patent creates composite peptide structures by combining conventional cyclic peptide frameworks with modified amino acid residues and alternative cyclization motifs, achieving enhanced stability through structural complexity that resists enzymatic and chemical degradation
2Duration of action of stationary object
If conventional cyclic peptides are used, then they can be prepared through automated synthesis, but they have limited in vivo retention time
Solution Approach 1:
The patent extends in vivo retention time by modifying peptide physical-chemical parameters including molecular weight, hydrophobicity, and conformational flexibility through altered cyclization patterns and amino acid substitutions that reduce renal clearance and improve metabolic stability
3Reliability
If cyclic peptide structure is used, then conformational restrictions improve binding stability, but the structure becomes more complex
Solution Approach 1:
The patent optimizes binding stability by adjusting conformational restriction parameters through varying cyclization positions and introducing flexible linkers or rigidifying groups that enhance target binding without excessive structural complexity
Solution Approach 2:
The patent divides the cyclic peptide structure into modular segments with distinct functional regions - targeting moieties, linker regions, and cyclization elements - allowing independent optimization of binding stability versus synthetic complexity
Data Source
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Figure 3A~3B
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.