Protegrin Peptide Polymer Conjugates for Half-Life Extension
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Solution Overview
Problem
Native protegrin peptides have a short in vivo half-life, making them impractical for administration due to rapid clearance, and there is a need for modified forms with enhanced stability and prolonged activity.
Innovation Solution
Development of releasable protegrin peptide polymer conjugates, where a protegrin moiety is covalently attached to water-soluble polymers like mPEG, enhancing stability and prolonging the peptide's presence in the body while maintaining therapeutic effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If native protegrin peptides are administered, then therapeutic activity is achieved, but in vivo half-life is short due to rapid clearance
Solution Approach 1:
The patent applies composite materials by conjugating protegrin peptides with water-soluble polymers (such as polyethylene glycol, polyvinyl alcohol, or dextran) to create a hybrid molecule. This composite structure combines the therapeutic properties of protegrin with the extended circulation characteristics of the polymer, thereby prolonging in vivo half-life and reducing renal clearance while maintaining antimicrobial activity.
2Stability of the object's composition
If protegrin peptides are modified to extend half-life, then stability is improved, but complexity of modification increases
Solution Approach 1:
The patent employs parameter changes by systematically varying the type, molecular weight, and degree of polymer conjugation to optimize the balance between stability enhancement and structural simplicity. By adjusting these parameters, the invention achieves extended half-life through relatively straightforward conjugation chemistry rather than complex peptide engineering, maintaining stability while controlling modification complexity.
Data Source
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AI summary
The invention provides protegrin that are chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention has enhanced half-life and/or reduced clearance.