Proper assessment of protein stability is not only worthwhile but necessary. Those who carefully evaluate the quality of their protein samples and optimize preparative workflows improve their chances of successful outcomes. This is especially the case in areas of biologic drug development, bioprocessing, crystallography, protein expression, and purification. Proteins are easily susceptible to loss of stability, leading to misfolding, degradation, aggregation, and inactivity. In order to meet regulations, protein products must be proven to be stable not only within the body but also in manufacturing and storage.
The realm of protein stability can be nuanced and specialized depending on the end product. To help, here is a list of resources offering guidance and bioanalytical strategies from multiple perspectives:
This review presents a step-by-step workflow of common physical and chemical methods that can be used to check for the following protein properties: purity and integrity, homogeneity and activity. To ensure retention of protein activity, tips for optimizing protein storage are also included.
In protein crystallization, stability is a fundamental prerequisite. This review presents protein stability from a structural biology viewpoint, distinguishing between two key concepts: compositional stability and conformational stability. It also covers strategies for protein expression, purification, and crystallization.
This informative handbook sets guiding principles to evaluate vaccine stability for the sake of clinical trial approval, licensing, and post-licensure monitoring. Considerations in topics such as stability parameters, frequency of testing, study design, and data analysis are discussed.
4. Guideline for Industry: Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products from the U.S. Food and Drug Administration
Proteins are susceptible to the elements, including temperature change, oxidation, light, ionic content, and mechanical stress. If not stored properly, biological products can lose their activity or degrade. This document (which is old, but still relevant) provides useful study guidelines for assessing long-term stability in support of a successful product.
In some instances, engineered proteins have been observed to suffer from low stability and expression levels. This paper reviews recent computational phylogenetic and structure-modeling approaches for protein stability design. The overarching objective is to advance the rational engineering of improved enzymes, therapeutics, and vaccines.
To learn more, check out this eBook for characterizing protein stability. A special emphasis is placed on the latest tools and technologies available for assessing key stability parameters.