| Summary: | 碩士 === 國立中央大學 === 化學工程與材料工程研究所 === 99 === With the rapid development of biotechnology and genetic engineering over this decade, peptide drug synthesis has precisely controlled to become an important direction for searching and developing of lead compounds in pharmaceutical companies. The market capitalization of peptide drugs was estimated about ?11.5 billion until 2013. The solid-phase peptide synthesis (SPPS) gave a strong impetus to the therapeutic peptide field. However, the peptide purification process usually dominated the overall cost. Also, the synthetic peptides often contained impurities due to amino acid deletion or insertions; in particular, enantiomeric impurities arising from racemization during peptide synthesis. The almost similar physical and chemical properties between impurity and desired peptides were the major problems for peptide separation. Therefore, the optimization of peptide purification process was to be an important course for minimizing the cost. In this study, the solubility parameter (δ) theory was utilized to build up an optimization strategy for peptide purification by HPLC. Under the experimental and theoretical methods, we hope to predict and descript the retention behaviors of peptide in column. This thesis is divided into three parts: First, to determine the solubility parameter of analyte (peptide), mobile phase (solvent) and stationary phase (column) in HPLC system; then, to find the proper ranging of mobile phase and composition; finally, to combine the solubility parameter calculation and molecular dynamics simulation for isomer separation. The results revealed that the isomers could be separated by transferring from one binary mobile phase to an iso-eluotropic (the same eluotropic strength) binary mixture arisen from different solubility parameter, and owned a good enantiomer separation.
|
|---|
