Evaluation of statistical design/modeling for prediction of the effect of amino acids on agitation-induced aggregation of human growth hormone and human insulin
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This study investigated how the physical-chemical characteristics of natural amino acids influence the conformational stability of recombinant human growth hormone (rhGH) and hexameric recombinant human insulin. A statistical design, with a set of physical-chemical descriptors, was used to ensure selection of natural amino acids having a wide range of properties. Amino acids were found to affect agitation induced aggregation of rhGH, as well as insulin. Of particular interest, a substantial stabilization of rhGH occurred in the presence of arginine. In contrast, insulin was destabilized in the presence of all the amino acids selected. A model correlating amino acid physicochemical properties and rhGH agitation-induced aggregation was established. However, no such model could be constructed for the insulin stability data. Thus, it remains questionable whether a simple set of physical-chemical descriptors can sufficiently reflect the general impact of amino acids on the delicate balance of forces needed to maintain protein physical stability.
|Journal||Journal of Drug Delivery Science and Technology|
|Number of pages||8|
|Publication status||Published - 2005|
- Agitation-induced aggregation, Amino acids, FTIR, Human growth hormone, Human insulin