Evaluation of statistical design/modeling for prediction of the effect of amino acids on agitation-induced aggregation of human growth hormone and human insulin

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 - STP pharma sciences

JF - STP pharma sciences

IS - 6

ER -