Investigation Into Efficiency of a Novel Glycol Chitosan-Bestatin Conjugate to Protect Thymopoietin Oligopeptides From Enzymatic Degradation
文献类型：期刊论文
| 作者 | Li, Wenzhao2; Li, Chunlei3; Shi, Nianqiu2,6; Kong, Wei1,2; Chen, Yan1,2; Zhang, Yong1,2,3; Feng, Jiao1; Cui, Lili4,7; Zhang, Yuebin5 |
| 刊名 | JOURNAL OF PHARMACEUTICAL SCIENCES
 |
| 出版日期 | 2016-02-01 |
| 卷号 | 105期号:2页码:828-837 |
| 关键词 | Thymopoietin Oligopeptides Degradation Clearance Aminopeptidase Inhibitor Chitosan Conjugation Peptide Kinetics |
| ISSN号 | 0022-3549 |
| DOI | 10.1002/jps.24567 |
| 文献子类 | Article |
| 英文摘要 | 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 of three 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 3 peptides from aminopeptidase-mediated 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 3 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. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved. |
| WOS关键词 | LAMININ-RELATED PEPTIDE ; LEUCINE AMINOPEPTIDASE ; BIOLOGICAL-ACTIVITY ; THYMOCARTIN TP4 ; ORAL DELIVERY ; THYMOPENTIN ; NANOPARTICLES ; ENHANCEMENT ; PENTAPEPTIDE ; INHIBITION |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000381768500049 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/170012]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 通讯作者 | Chen, Yan; Zhang, Yong |
| 作者单位 | 1.Jilin Univ, Sch Life Sci, Natl Engn Lab AIDS Vaccine, Changchun 130012, Peoples R China 2.Jilin Univ, Sch Life Sci, Key Lab Mol Enzymol & Engn, Minist Educ, Changchun 130012, Peoples R China 3.China Shijiazhuang Pharmaceut Grp Co Ltd, State Key Lab New Pharmaceut Preparat & Excipient, Shijiazhuang 050051, Peoples R China 4.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Peoples R China 5.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Dalian 116023, Peoples R China 6.Jilin Med Coll, Sch Pharm, Dept Pharmaceut, Jilin 132013, Peoples R China 7.Silence Therapeut GmbH, Robert Rossle Str 10, D-13125 Berlin, Germany |
| 推荐引用方式 GB/T 7714 | Li, Wenzhao,Li, Chunlei,Shi, Nianqiu,et al. Investigation Into Efficiency of a Novel Glycol Chitosan-Bestatin Conjugate to Protect Thymopoietin Oligopeptides From Enzymatic Degradation[J]. JOURNAL OF PHARMACEUTICAL SCIENCES,2016,105(2):828-837. |
| APA | Li, Wenzhao.,Li, Chunlei.,Shi, Nianqiu.,Kong, Wei.,Chen, Yan.,...&Zhang, Yuebin.(2016).Investigation Into Efficiency of a Novel Glycol Chitosan-Bestatin Conjugate to Protect Thymopoietin Oligopeptides From Enzymatic Degradation.JOURNAL OF PHARMACEUTICAL SCIENCES,105(2),828-837. |
| MLA | Li, Wenzhao,et al."Investigation Into Efficiency of a Novel Glycol Chitosan-Bestatin Conjugate to Protect Thymopoietin Oligopeptides From Enzymatic Degradation".JOURNAL OF PHARMACEUTICAL SCIENCES 105.2(2016):828-837. |
入库方式： OAI收割
来源：大连化学物理研究所
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