Cancer Peptide Therapeutics Targeting caPCNA Isoforms
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Solution Overview
Problem
Current therapies lack effective methods to selectively inhibit cancer cell proliferation by targeting cancer-specific isoforms of proliferating cell nuclear antigen (PCNA), which are unique to malignant cells, without affecting non-malignant cells.
Innovation Solution
Development of peptide variants derived from specific regions of cancer-specific PCNA that interfere with the interaction of cellular proteins with PCNA, including amino acid substitutions and cell-permeable sequences to enhance cytotoxic effects, which can be administered alone or in combination with chemotherapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapeutic agents are used to inhibit cancer cell proliferation, then cancer cell growth is suppressed, but non-malignant cells are also affected causing harmful side effects
Solution Approach 1:
The patent applies local quality by designing peptides with specific amino acid sequences that recognize and bind only to the cancer-specific PCNA isoform (caPCNA) with altered isoelectric point, while leaving non-malignant PCNA unaffected. This localized specificity at the molecular level enables selective cancer cell inhibition without harming normal cells
Solution Approach 2:
The invention exploits parameter changes in the PCNA protein's isoelectric point between cancer and non-malignant forms. By targeting this specific biophysical parameter difference, the peptides achieve selective binding to caPCNA, resolving the contradiction between effective cancer cell suppression and preservation of non-malignant cell function
2Reliability
If peptide variants with enhanced cytotoxic effects are developed, then cancer cell proliferation is more effectively inhibited, but the complexity of peptide design and manufacturing increases
Solution Approach 1:
The patent segments the complex problem of cancer cell inhibition into modular peptide components with specific amino acid sequences. Each peptide variant is designed as a discrete molecular entity targeting a specific region of PCNA, simplifying the design process while maintaining high efficacy through combinatorial optimization of sequence variants
Solution Approach 2:
The invention uses copying by creating multiple peptide variants based on a core sequence template that targets caPCNA. These variants are generated through systematic amino acid substitutions and modifications, allowing efficient exploration of structure-activity relationships without requiring de novo design of each peptide
Data Source
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AI summary
Peptide variants corresponding to cancer specific isoform of proliferating cell nuclear antigen (caPCNA) interfere with intracellular protein-protein interaction, thereby causing a reduction in the proliferative potential of cancer. Cell-permeable caPCNA-derived peptides and their variants serve as therapeutic compositions to reduce the proliferation of cancer cells and also augment cytotoxic effects of existing cancer therapy. These compositions are also useful for chemoprevention of cancer.