Cell-Permeable Cyclic Peptide Scaffolds for Undruggable Targets
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Solution Overview
Problem
Current small molecule drugs are limited in targeting undruggable proteins due to lack of well-defined binding pockets, restricting their therapeutic potential across various disease categories.
Innovation Solution
Development of cell-permeable cyclic peptide scaffolds, specifically hexapeptides composed of naturally or non-naturally occurring amino acids, which can interact with undruggable targets like transcription factors and non-coding RNAs, enhancing therapeutic accessibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If small molecule drugs are used to target undruggable proteins, then the drug size and complexity are limited, but the ability to effectively bind to targets without well-defined binding pockets is insufficient
Solution Approach 1:
The patent applies parameter changes by transitioning from small molecule drugs to cyclic peptide scaffolds, fundamentally altering the size, complexity, and structural parameters of the therapeutic agent. This enables the drug to adapt to undruggable targets like transcription factors and non-coding RNAs that lack well-defined binding pockets, thereby resolving the contradiction between drug complexity and target accessibility
2Reliability
If cyclic peptides are synthesized to improve potency and proteolytic stability, then therapeutic potential against undruggable targets increases, but cell permeability becomes limited
Solution Approach 1:
The patent applies local quality by incorporating specific cell-permeable motifs (such as cell-penetrating peptides or transduction domains) into the cyclic peptide scaffold at strategic locations. This allows the peptide to maintain its proteolytic stability and potency while acquiring the local property of cell permeability, thereby resolving the contradiction between stability and ease of cellular uptake
Data Source
AI summary
Aspects of the present disclosure include cell permeable cyclic peptide scaffolds that include a hexapeptide composed of naturally or non-naturally occurring amino acids. Pharmaceutical compositions having one or more of the cell permeable cyclic peptide scaffolds and pharmaceutically acceptable excipient are also provided. Methods for using the subject cell permeable cyclic peptide scaffolds are also described.