Cyclic Cell-Penetrating Peptide Composition for Cytosolic Delivery
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Solution Overview
Problem
Traversing the plasma membrane poses a significant challenge for delivering biologics such as peptides, proteins, and nucleic acids into cells, with endosomal membranes acting as a barrier to cytoplasmic delivery by cell-penetrating peptides (CPPs).
Innovation Solution
Development of cyclic peptides comprising at least two arginines and either one non-aromatic hydrophobic or one hydrophobic side chain, which enhance cytosolic delivery efficiency without relying on two hydrophobic aromatic side chains.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cell-penetrating peptides use two hydrophobic aromatic side chains to traverse the plasma membrane, then membrane penetration is achieved, but the endosomal membrane barrier prevents cytoplasmic delivery
Solution Approach 1:
The patent changes the chemical parameters of the peptide by replacing two hydrophobic aromatic side chains with a specific combination of at least one hydrophobic side chain (aromatic or non-aromatic) and at least one charged side chain (arginine, lysine, or histidine). This parameter change allows the peptide to overcome the endosomal membrane barrier while maintaining plasma membrane penetration capability, thereby achieving reliable cytoplasmic delivery.
Solution Approach 2:
The invention creates a composite peptide structure combining different functional elements: hydrophobic side chains for membrane insertion, charged side chains (arginine, lysine, or histidine) for interacting with the endosomal membrane barrier, and cyclic backbone structure for stability. This composite approach enables simultaneous traversal of both plasma membrane and endosomal membrane barriers.
2Reliability
If cyclic peptides are designed with at least one hydrophobic and one charged side chain, then endosomal barrier is overcome, but the structural complexity increases
Solution Approach 1:
The patent applies local quality by concentrating specific functional properties at particular locations within the peptide structure. The cyclic backbone provides structural stability, while specific residues (at least one hydrophobic and one charged side chain) are positioned to interact with specific barriers. This localized functional distribution achieves effective barrier penetration without requiring complex overall structure.
3Speed
If the peptide uses arginine-rich sequences to interact with membranes, then membrane traversal is facilitated, but the peptide may be degraded by proteases
Solution Approach 1:
The patent segments the peptide function into distinct elements: the cyclic backbone structure provides stability and resistance to proteolytic degradation, while specific arginine-rich segments provide membrane interaction capability. This segmentation allows each element to perform its specialized function without compromising the other, maintaining both traversal rate and stability.
Data Source
AI summary
Disclosed are cell penetrating peptides and compositions comprising such peptides that can be used to deliver agents to various cell types.