PSMA Targeting Ligands with Helical Peptides for Larger Payload Delivery
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Solution Overview
Problem
Existing PSMA-targeting ligands are limited in their ability to deliver larger active molecules, such as proteins or protein complexes, to prostate cancer sites, and there is a need for ligands with enhanced binding affinity and ease of conjugation to other therapeutic agents.
Innovation Solution
Development of PSMA targeting ligands with high affinity, incorporating a urea-linked di-amino acid structure and a peptide portion that can form a helical structure, allowing for enhanced attachment of additional groups through a conjugation handle, such as therapeutic proteins, nanoparticles, or imaging agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing PSMA-targeting ligands are used to deliver larger active molecules such as proteins or protein complexes, then the delivery capability is limited, but using ligands with enhanced binding affinity could improve delivery efficiency
Solution Approach 1:
The patent modifies the chemical structure of PSMA-targeting ligands by incorporating urea-linked di-amino acid structures and helical peptide portions, which changes the binding parameters and enhances affinity for PSMA. This structural parameter change enables more effective delivery of larger therapeutic molecules.
Solution Approach 2:
The patent creates composite structures by combining the PSMA-targeting ligand core with additional functional groups, therapeutic agents, or imaging agents through conjugation. This composite approach allows the ligand to maintain its targeting capability while delivering larger and more complex therapeutic payloads.
2Reliability
If PSMA targeting ligands are designed with enhanced binding affinity, then delivery capability improves, but the complexity of conjugation to other therapeutic agents may increase
Solution Approach 1:
The patent designs the ligand structure with universal features that can accommodate multiple types of therapeutic agents and imaging agents. The standardized core structure with defined conjugation points allows the same ligand platform to be used for delivering various payloads, reducing overall conjugation complexity despite enhanced binding requirements.
3Reliability
If PSMA targeting ligands incorporate complex structures for enhanced affinity, then binding capability improves, but the ease of conjugation to additional groups may be reduced
Solution Approach 1:
The patent introduces intermediary conjugation handles or linkers that facilitate the attachment of therapeutic agents to the PSMA-targeting ligand. These intermediary structures serve as chemical mediators that simplify the conjugation process while preserving the enhanced binding capability of the core ligand structure.
Data Source
AI summary
The present disclosure relates to ligands capable of binding to PSMA. Such ligands are useful for attaching to additional groups (e.g., payloads, such as proteins or radionuclides) in order to target the additional groups to cells expressing PSMA (e.g., prostate cancer cells).