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Stability of protein pharmaceuticals
M C Manning1, K Patel, R T Borchardt
1Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
Pharmaceutical Research
|November 1, 1989
Summary
Recombinant DNA technology enables pharmaceutical protein production, but protein instability presents challenges. Strategies like additives and mutagenesis enhance protein stability for drug development.
Area of Science:
- Biotechnology
- Pharmaceutical Science
- Protein Chemistry
Background:
- Recombinant DNA technology facilitates the production of pharmaceutical proteins.
- Biotech-derived proteins are a significant part of drug development pipelines.
- Proteins' unique properties present challenges in isolation, purification, formulation, and delivery.
Purpose of the Study:
- To summarize protein decomposition pathways (chemical and physical).
- To present current methodologies for stabilizing pharmaceutical proteins.
Main Methods:
- Review of chemical instability pathways: proteolysis, deamidation, oxidation, racemization, beta-elimination.
- Review of physical instability processes: aggregation, precipitation, denaturation, adsorption.
- Overview of stabilization techniques: additives, excipients, chemical modification, site-directed mutagenesis.
Main Results:
- Detailed description of various chemical and physical degradation routes for proteins.
- Identification of key challenges in maintaining protein integrity throughout pharmaceutical processes.
- Compilation of existing strategies to mitigate protein instability.
Conclusions:
- Understanding protein decomposition is crucial for pharmaceutical applications.
- Multiple methods exist to improve the stability of therapeutic proteins.
- Site-directed mutagenesis offers a route to engineer more stable protein variants.