The secondary structure and aggregation of lyophilized tetanus toxoid

被引:43
作者
Costantino, HR
Schwendeman, SP
Griebenow, K
Klibanov, AM
Langer, R
机构
[1] MIT,DEPT CHEM,CAMBRIDGE,MA 02139
[2] MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139
关键词
D O I
10.1021/js960148+
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Tetanus toroid (TT), the vaccine for tetanus, is an important protein antigen and candidate for sustained release from polymeric matrices. During administration from the latter, the solid (e.g., lyophilized) protein will be exposed to elevated levels of temperature and moisture, conditions which trigger its aggregation. To examine the connection between this aggregation and the structure of the TT molecule in the solid state, Fourier-transform infrared (FTIR) spectroscopy was employed to determine the secondary structure of TT in the presence of various excipients. We found that excipient-free TT undergoes a significant alteration (mostly reversible) in the secondary structure during lyophilization. Specifically, more than half the total alpha-helix content was lost with a concomitant increase in beta-sheet structure. The extent of structural alterations in the presence of 1:5 (g:g protein) NaCl, sorbitol, or poly(ethylene glycol), did not correlate with stability conferred towards moisture-induced aggregation. These results suggest that the degree of retention of the native protein structure in the dry state is not a general predictor of stability for the ''wetted'' solid within polymer controlled-release vehicles.
引用
收藏
页码:1290 / 1293
页数:4
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