Cyclic Synthetic Peptide Blocks CD40:CD154 Interaction
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Solution Overview
Problem
Current approaches to inhibit the CD40:CD154 interaction, such as anti-CD154 monoclonal antibodies, face limitations including immunogenic effects, prothrombotic side effects, poor tissue penetration, and immunosuppression, which compromise their efficacy in treating autoimmune diseases and other conditions.
Innovation Solution
A synthetic peptide, specifically designed to bind to the active site of human CD154, inhibiting the interaction between CD40 and CD154, is developed. This peptide is cyclic or multimeric, allowing for enhanced stability and reduced immunogenicity, and can be used in both therapeutic and diagnostic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-CD154 monoclonal antibodies are used to inhibit the CD40:CD154 interaction, then the interaction is effectively blocked, but immunogenic effects and prothrombotic side effects occur
Solution Approach 1:
The patent extracts only the essential binding function from the complete monoclonal antibody structure by using synthetic peptides that specifically target the CD154 active site. This extraction eliminates the Fc fraction responsible for immunogenic effects and prothrombotic side effects while preserving the blocking capability against CD40:CD154 interaction
Solution Approach 2:
The patent creates simplified copies of the antibody's binding function using synthetic peptides (SEQ ID NO:6 and SEQ ID NO:13) that replicate the essential interaction with CD154. These peptide copies maintain the therapeutic effect of blocking CD40:CD154 interaction without the harmful immunogenic properties of full antibodies
2Reliability
If monoclonal antibodies are used to block CD40:CD154 interaction, then therapeutic effect is achieved, but poor tissue penetration occurs
Solution Approach 1:
The patent segments the large monoclonal antibody molecule into smaller synthetic peptide units (7-30 amino acids). This segmentation reduces molecular size and increases tissue penetration capability while maintaining the essential CD154 binding function through optimized peptide sequences
3Reliability
If monoclonal antibodies are used to inhibit CD40:CD154 interaction, then immune response is modulated, but immunosuppression occurs
Solution Approach 1:
The patent changes the molecular parameters from large antibody molecules to small synthetic peptides, which alters the pharmacological profile. The peptide format provides immune response modulation through CD40:CD154 blockade without the excessive immunosuppression associated with full antibody therapy, due to differences in half-life, distribution, and mechanism of action
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 peptide effectively blocks the CD40:CD154 interaction, preventing B cell activation, isotype switching, and endothelial cell stimulation, while avoiding unwanted immune responses and platelet aggregation, thus offering a safer and more effective alternative for treating inflammatory and autoimmune diseases.
Implementation Method 1
a synthetic peptide which is capable of binding to human CD40 ligand (CD40L or CD154)... specifically binding to the active site of CD154
Data Source
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AI summary
The invention refers to a synthetic peptide comprising an amino acid sequence of seven residues in length, preferably flanked by 2 cysteine residues at both ends, which is capable of specifically recognizing human CD154 and blocking CD40:CD154 interaction, thereby inhibiting the biological effects depending on such interaction. The peptide of the invention, which is preferably in a cyclic form, is suitable for use for diagnostic and therapeutic applications, especially for the diagnosis and therapy of tumor, inflammatory diseases and transplant rejection.