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Investigation into efficiency of a novel glycol chitosan-bestatin conjugate to protect thymopoietin oligopeptides from enzymatic degradation.  
Investigation into efficiency of a novel glycol chitosan-bestatin conjugate to protect thymopoietin oligopeptides from enzymatic degradation.
資料類型: PDF文件
關鍵詞: thymopoietin  oligopeptides  degradation  clearance  aminopeptidase  inhibitor  chitosan  
conjugation  peptide  kinetics  
資料大小: 650k
所屬學科: 通用高分子材料
來源: 來源網(wǎng)絡
簡介:
In this study, a novel glycol chitosan (GCS)–bestatin conjugate was synthesized and evaluated to demonstrate its efficacy in protecting thymopoietin oligopeptides from aminopeptidase-mediated degradation. Moreover, the mechanism and relative susceptibility ofthree thymopoietin oligopeptides, thymocartin (TP4), thymopentin (TP5), and thymotrinan (TP3), to enzymatic degradation were investigated and compared at the molecular level. Initial investigations indicated that formation of the GCS–bestatin conjugate, with a substitution degree of 7.0% (moles of bestatin per mole of glycol glucosamine unit), could significantly protect all three peptides from aminopeptidasemediated degradation in a concentration-dependent manner. The space hindrance and loss of one pair of hydrogen bonds, resulting from the covalent conjugation of chitosan with bestatin, did not affect the specific interaction between bestatin and aminopeptidase. Moreover, TP4 displayed a higher degradation clearance compared with those of TP5 and TP3 under the same experimental conditions. The varying levels of susceptibility of these three peptides to aminopeptidase (TP4 > TP5 > TP3) were closely related to differences in their binding energies to enzyme, which mainly involved Van der Waals forces and electrostatic interactions, as supported by the results of molecular dynamics simulations. These results suggest that GCS–bestatin conjugate might be useful in the delivery of thymopoietin oligopeptides by mucosal routes, and that TP3 and TP5 are better alternatives to TP4 for delivery because of their robust resistance against enzymatic degradation.
上傳人: shinianqiu
上傳時間: 2017-04-14 13:07:49
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