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Supramolecular Protein Stabilization with Zwitterionic Polypeptide-Cucurbit[7]uril Conjugates.
Zachary S Clauss1, Rolande Meudom2, Bo Su3
1Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah 84112, United States.
Biomacromolecules
|December 13, 2022
Summary
New zwitterionic polypeptides conjugated with cucurbit[7]uril effectively prevent protein aggregation in biopharmaceuticals. These biodegradable and non-toxic materials offer a promising solution for stabilizing protein therapeutics like insulin and calcitonin.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Biopharmaceutical Development
Background:
- Protein aggregation poses significant challenges for biopharmaceutical development, impacting drug stability, shipping, and storage.
- Existing stabilization methods often lack biodegradability, non-toxicity, or high efficiency.
- There is a critical need for novel, simple, and effective materials to stabilize protein therapeutics.
Purpose of the Study:
- To investigate zwitterionic polypeptides conjugated to cucurbit[7]uril as a novel strategy for inhibiting protein aggregation.
- To evaluate the efficacy of these conjugates in stabilizing model protein therapeutics, insulin and calcitonin.
- To assess the biodegradability and cytotoxicity of the developed zwitterionic polypeptide-based system.
Main Methods:
- Rapid and scalable polymerization techniques were used to synthesize zwitterionic polypeptides based on methionine.
- Polypeptides were end-modified with cucurbit[7]uril macrocycles for supramolecular binding to proteins.
- Aggregation inhibition was tested using model proteins insulin and calcitonin.
- Cytotoxicity was assessed in human cells, and biodegradation was evaluated using natural proteases.
Main Results:
- Zwitterionic polypeptide-cucurbit[7]uril conjugates of sufficient chain length efficiently inhibited insulin aggregation.
- These conjugates also demonstrated efficacy in inhibiting calcitonin aggregation.
- The developed polypeptides showed no cytotoxicity in human cells at concentrations five-fold higher than therapeutic levels.
- Biodegradation of zwitterionic polypeptides was observed upon treatment with natural proteases.
Conclusions:
- Zwitterionic polypeptides conjugated with cucurbit[7]uril represent a highly efficient and promising approach for stabilizing protein therapeutics.
- The system is biodegradable and non-toxic, addressing key limitations of current biopharmaceutical stabilization strategies.
- This novel material offers a potential solution for improving the shelf-life and delivery of vital protein-based medicines.
