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Protein nano- liposomes during active protection research
Author: SunZhuan
Tutor: GeZhiQiang
School: Tianjin University
Course: Pharmaceutical Engineering
Keywords: Protein Liposomes Active protection Protein Structure Molecular modeling
CLC: TQ464.7
Type: Master's thesis
Year: 2010
Downloads: 133
Quote: 0
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Abstract
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To study protein and peptide drugs in the formulation process and mechanism of activity , reduction of drug in the formulation process loss of activity , this article was prepared as a model drug trypsin Nanoliposomes , the preparation process of the activity of trypsin and add four active blocking agent protein activity , by detecting changes in protein structure and molecular dynamics simulation to investigate the protective agent to protect the mechanism of protein activity . 1, using the reverse evaporation method trypsin nanoliposomes particle size 160nm, encapsulation efficiency was 47%, Zeta potential -58mv; trypsin in liposomes loss of activity during 37% of the original protein , four kinds of protective agent activity in the protective effect of PEG on the best , make the activity retained 46% of the original protein , is a good protective agent . 2, using circular dichroism and Fourier transform infrared spectroscopy study of trypsin in the formulation process of the secondary structure changes , the application of fluorescence spectra of three protein structural changes . Circular dichroism shows trypsin at the nanoscale liposomes during their secondary structure in α- helix content from 18.7 % to 13.2%, β- fold and β- angle decrease from 15.6% , and 27.0 % to 20.3 percent and 31.9 percent , the results show the same trend IR . Fluorescence data indicate that the organic solvent treatment increased fluorescence protein , prepared liposomes decreased fluorescence molecules is more compact . Four protection agent is added in the secondary structure of the protein can be retained , wherein the PEG best protective effect , but little influence on tertiary structure . 3 , the use of amber software flexX docking and protective agents of the most simple molecular arginine and trypsin active sites of the molecular docking and molecular simulation, the arginine and the mechanism of action of trypsin . The results showed that arginine into trypsin activity in the cavity , and with seven pairs can form hydrogen bonds , a combination that is very strong , in theory, can maintain the three-dimensional structure of protein activity cavity , the cavity being protective activity of external factors of the change. The results show that the protective agent may be by preventing trypsin liposome secondary structure in the process , to reduce protein activity loss during preparation .
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CLC: > Industrial Technology > Chemical Industry > Pharmaceutical chemical industry > Drug production of biological products > Amino acids,peptides,proteins
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