TY - JOUR
T1 - Evaluation of statistical design/modeling for prediction of the effect of amino acids on agitation-induced aggregation of human growth hormone and human insulin
AU - Soenderkaer, S.
AU - Van De Weert, M.
AU - Lindgaard Hansen, L.
AU - Flink, J.
AU - Frokjaer, S.
PY - 2005/11/1
Y1 - 2005/11/1
N2 - 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.
AB - 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.
KW - Agitation-induced aggregation
KW - Amino acids
KW - FTIR
KW - Human growth hormone
KW - Human insulin
UR - http://www.scopus.com/inward/record.url?scp=28144453887&partnerID=8YFLogxK
M3 - Journal article
AN - SCOPUS:28144453887
SN - 1157-1489
VL - 15
SP - 427
EP - 434
JO - Journal of Drug Delivery Science and Technology
JF - Journal of Drug Delivery Science and Technology
IS - 6
ER -