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.

Original languageEnglish
JournalJournal of Drug Delivery Science and Technology
Issue number6
Pages (from-to)427-434
Number of pages8
Publication statusPublished - 2005

    Research areas

  • Agitation-induced aggregation, Amino acids, FTIR, Human growth hormone, Human insulin

ID: 198780053