| dc.description.abstract | In recent years, protein and peptide drugs play an important role in pharmaceutical industry. Unfortunately, these protein and peptide drugs are proteolytically instable in human serum resulting in short circulation half-life. A new product through grafting the polyethylene glycol (PEG), a well-known biocompatible polymer, with protein and peptide drugs is able to avoid clearance of kidney or attack of immune system, thus prolong the circulating half-life time. However, for the PEGylated protein and peptide drugs, the positional isomers are usually formed with random PEGylation. The chromatographic purification process of PEGylated protein and peptide drugs is still without a general guideline to carrier out, in particular for the role of PEG in protein and peptide drugs. In this study, we use Teriparatide as a model peptide drug, investigating the effect of PEGylation on the interactions between PEGylated peptide and hydrophobic surface. Teriparatide, a peptide drug for treating to osteoporosis by once-daily injection, is the 1-34 segment of recombinant human parathyroid hormone. After PEGylation, we found that the retention time increase and we determine the thermodynamic parameters between peptides and hydrophobic surface by reversed-phase chromatography. From the results, we concluded that the PEG chain will expose to the solution phase when the N- or C-PEG-Teriparatide adsorbed to the hydrophobic surface, resulting in numerous hydration reactions. In the contrary, when the Lys13-PEG-Teriparatide adsorbed to the hydrophobic surface, PEG chain will attach to the hydrophobic surface, release the water molecules, leading to increase the entropy of system. In addition, from the results of circular dichroism, the secondary structure of PEGylated Teriparatides are stronger than native Teriparatide in 30% ACN. Therefore, Teriparatide is more soluble in this condition, lead to the weaker binding strength between peptide and hydrophobic surface. Furthermore, the structure of Teriparatide in different solution conditions will change more than PEGylated Teriparatides. We are able to consider that PEGylated Teriparatides are more rigid. | en_US |