High Density Brush Polymers for Peptide Proteolytic Protection
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Solution Overview
Problem
Peptides used as therapeutics face challenges due to rapid proteolytic digestion and renal clearance, limiting their in vivo duration and bioavailability, and existing strategies for protection often compromise their functional integrity or require complex synthesis processes.
Innovation Solution
The development of high-density brush polymers through ring-opening metathesis polymerization (ROMP) to package peptides, which protects them from proteolysis while maintaining their biological function, and the use of cell-penetrating peptides and drug delivery vehicles to enhance bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemical modification of peptide is used to protect from proteolysis, then proteolytic resistance is improved, but peptide functional integrity may be compromised
Solution Approach 1:
The patent uses a polymer scaffold as an intermediary carrier that displays multiple peptide copies without chemically modifying the peptides themselves. The scaffold protects peptides from proteolysis through steric shielding and rapid diffusion away from protease active sites, while maintaining peptide native structure and function.
Solution Approach 2:
Instead of modifying a single peptide molecule, the patent creates multiple copies of the peptide and displays them on a polymer scaffold. This amplifies the protective effect against proteolysis while maintaining the original peptide sequence and biological activity intact.
2Reliability
If multiple conjugation and purification steps are used to create protected peptide structures, then proteolytic protection is improved, but synthesis complexity increases
Solution Approach 1:
The patent segments the synthesis process into two independent stages: first synthesizing the peptide-monomer conjugate with simple chemistry, then polymerizing the monomer to form the final protected structure. This avoids complex multi-step conjugation and purification procedures while achieving effective proteolytic protection.
3Quantity of substance
If peptide molecular weight is kept low for renal clearance, then bioavailability is improved, but duration of action decreases
Solution Approach 1:
The patent merges multiple low-molecular-weight peptide copies onto a single polymer scaffold, creating a high-molecular-weight complex that resists renal clearance. This combination achieves both bioavailability (through peptide activity) and extended duration of action (through reduced clearance and proteolytic resistance).
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
The approach provides a general and accessible method for creating proteolytically resistant peptide displays that maintain their intended functions, such as receptor binding or therapeutic effects, with improved bioavailability and cellular uptake.
Implementation Method 1
The graft-through polymerization of norbornyl-peptide monomers via ROMP can result in structures that resist proteolysis
Data Source
AI summary
Described herein, inter alia, are peptide containing polymers, and methods of making and using the same.