Peptides Inhibiting RING E3 Enzymes for Hyperproliferative Disease
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Solution Overview
Problem
Current cancer therapies targeting RING finger domain-containing proteins like the anaphase-promoting complex/cyclosome (APC/C) face challenges due to their 'non-druggable' nature, leading to undesirable side effects and resistance, particularly in treating hyperproliferative and inflammatory diseases.
Innovation Solution
Development of specific peptides and peptidomimetics that bind to RING E3 enzymes, such as APC11, interfering with their function by competing with E2 enzyme recruitment, thereby inhibiting mitosis and offering a new avenue for treating hyperproliferative and inflammatory diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer therapies target RING finger domain-containing proteins like APC/C, then cell division can be inhibited, but the treatment causes undesirable side effects and resistance due to the 'non-druggable' nature of these targets
Solution Approach 1:
The patent uses peptides as intermediary molecules that specifically bind to the RING finger domain of E3 ubiquitin ligases. These peptides act as mediators between the therapeutic goal (inhibiting cell division) and the target protein (RING finger domain), providing selective inhibition without the harsh effects of conventional chemotherapy. The peptides compete with E2 enzymes for binding to the RING finger domain, thereby selectively blocking ubiquitin ligase activity while sparing other cellular processes.
Solution Approach 2:
The patent modifies the chemical parameters of the therapeutic agents by using peptide-based molecules with specific amino acid sequences and structures. These parameter changes (molecular structure, binding affinity, specificity) allow the therapy to target RING finger domains precisely, changing the interaction characteristics from non-specific (conventional chemo) to highly specific (peptide-based), thereby reducing side effects while maintaining efficacy.
2Productivity
If RING E3 enzymes are inhibited to treat hyperproliferative diseases, then cell proliferation can be controlled, but the 'non-druggable' nature of these targets makes effective inhibition difficult
Solution Approach 1:
The patent extracts and isolates the critical functional domain (RING finger domain) from the entire RING E3 enzyme complex. By focusing therapeutic intervention on this specific domain rather than attempting to inhibit the entire complex, the patent simplifies the drug target into a druggable unit. The peptides are designed to specifically bind to this extracted domain, making the previously non-druggable target accessible to pharmacological intervention.
Solution Approach 2:
The patent creates peptide copies or mimics of the natural binding interfaces that interact with RING finger domains. These peptide sequences are designed to replicate the binding characteristics of natural substrates or regulatory proteins, allowing them to compete effectively for binding to the RING finger domain. This copying approach enables the use of relatively simple peptide structures to achieve complex biological inhibition.
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 peptides and peptidomimetics effectively inhibit RING E3 function, including APC/C, providing a therapeutic approach to slow down or stop cell division and induce apoptosis, potentially overcoming resistance and side effects associated with existing treatments.
Implementation Method 1
peptides and peptidomimetics that bind to RING E3 enzymes, such as APC11, interfering with their function by competing with E2 enzyme recruitment
Data Source
AI summary
The present invention relates to peptides and peptidomimetics as well as their medical use in the treatment of hyperproliferative diseases and inflammatory diseases.