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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.

OriginalsprogEngelsk
TidsskriftJournal of Drug Delivery Science and Technology
Vol/bind15
Udgave nummer6
Sider (fra-til)427-434
Antal sider8
ISSN1157-1489
StatusUdgivet - 1 nov. 2005

ID: 198780053