聚乙二醇衍生物及其蛋白药物修饰研究进展

张羽; 连治国; 徐明波; 冯芳

doi:10.3969/j.issn.1006-0111.2018.04.004

聚乙二醇衍生物及其蛋白药物修饰研究进展

doi: 10.3969/j.issn.1006-0111.2018.04.004

1.
中国药科大学, 江苏南京 210009;北京双鹭药业股份有限公司, 北京 100041
2.
北京双鹭药业股份有限公司, 北京 100041
3.
中国药科大学, 江苏南京 210009

Advances in the development of PEG derivatives and pegylated protein drugs

1.
China Pharmaceutical University, Nanjing 210009, China;Beijing SL Pharmaceutical Co., Ltd., Beijing 100041, China
2.
Beijing SL Pharmaceutical Co., Ltd., Beijing 100041, China
3.
China Pharmaceutical University, Nanjing 210009, China

摘要: 聚乙二醇及其衍生物因其出色的亲水性、生物相容性、生物学惰性等特性而被广泛应用于蛋白药物修饰，其修饰可有效降低蛋白药物的免疫原性并延长体内半衰期。聚乙二醇衍生物的发展经历了第一代随机修饰，第二代特异性和功能性修饰，以及第三代分支型结构的应用。其应用也从简单的药物修饰扩展到生物传感、药物传输等方面。
- 聚乙二醇衍生物 /
- 聚乙二醇修饰 /
- 蛋白药物 /
- 长效
Abstract: Polyethylene glycol and its derivatives are widely used in protein drug modification due to the excellent hydrophilicity, biocompatibility and bioinertia. The pegylation makes it possible that protein has lower immunogenicity and longer half-life. PEG derivatives had undergone three generations, from random modifications, to site-specific and functional modifications, and then branched structures. The application of PEG derivatives also extends to biosensing and drug delivery. Advances in the development of PEG derivatives and pegylated protein drugs were reviewed in this paper.
- PEG derivatives /
- pegylation /
- protein drugs /
- long-acting

[1]	LAWRENCE P B, PRICE J L. How PEGylation influences protein conformational stability[J]. Curr Opin Chem Biol, 2016, 34:88-94.
[2]	PFISTER D, BOURGEAUX E, MORBIDELLI M. Kinetic modeling of protein PEGylation[J]. Chem Engin Sci, 2015, 137:816-827.
[3]	YANG Z, WANG J, LU Q, et al. PEGylation confers greatly extended half-life and attenuated immunogenicity to recombinant methioninase in primates[J]. Cancer Res, 2004, 64(18):6673-6678.
[4]	RODR GUEZMART NEZ JA, RIVERARIVERA I, SOL RJ, et al. Enzymatic activity and thermal stability of PEG-α-chymotrypsin conjugates[J]. Biotechnol Lett, 2009, 31(6):883-887.
[5]	姜忠义, 许松伟, 王艳强. 蛋白质和肽类分子的聚乙二醇化化学[J]. 有机化学, 2003, 23(12):1340-1347.
[6]	ZALIPSKY S, SELTZER R, MENONRUDOLPH S. Evaluation of a new reagent for covalent attachment of polyethylene glycol to proteins[J]. Biotechnol Appl Biochem, 1992, 15(1):100-114.
[7]	MIRON T, WILCHEK M. A simplified method for the preparation of succinimidyl carbonate polyethylene glycol for coupling to proteins[J]. Bioconjug Chem, 1993, 4(6):568-569.
[8]	ABUCHOWSKI A, KAZO GM, JR VC, et al. Cancer therapy with chemically modified enzymes. I. Antitumor properties of polyethylene glycol-asparaginase conjugates[J]. Cancer Biochem Biophys, 1984, 7(2):175-186.
[9]	ABUCHOWSKI A,VAN ES T,PALCZUK NC,et al. Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol[J]. J Biol Chem,1977,252(11):3578-3581.
[10]	GAIS H J, RUPPERT S. Modification and immobilization of proteins with polyethylene glycol tresylates and polysaccharide tresylates:Evidence suggesting a revision of the coupling mechanism and the structure of the polymer-polymer linkage[J]. Tetrahedron Lett, 1995, 36(22):3837-3838.
[11]	ZALIPSKY S, LEE C. Use of functionalized poly(ethylene glycol)s for modification of polypeptides[M]//Poly(Ethylene Glycol) Chemistry. Springer US, 1992:1-15.
[12]	WANG J, HU T, LIU Y, et al. Kinetic and stoichiometric analysis of the modification process for N-terminal PEGylation of staphylokinase[J]. Anal Biochem, 2011, 412(1):114-116.
[13]	KINSTLER OB, BREMS DN, LAUREN SL, et al. Characterization and stability of N-terminally PEGylated rhG-CSF[J]. Pharm Res, 1996, 13(7):996-1002.
[14]	KINSTLER OB, GABRIEL NE, FARRAR CE, et al. N-terminally chemically modified protein-compositions and method:, DE 69509628 D1[P]. 1999.
[15]	FEE C J, DAMODARAN VB. Production of PEGylated proteins[M]//Biopharmaceutical Production Technology. 2012:199-222.
[16]	BROCCHINI S, GODWIN A, BALAN S, et al. Disulfide bridge based PEGylation of proteins[J]. Adv Drug Deliv Rev, 2008, 60(1):3-12.
[17]	TSUTSUMI Y, ONDA M, NAGATA S, et al. Site-specific chemical modification with polyethylene glycol of recombinant immunotoxin anti-Tac(Fv)-PE38(LMB-2) improves antitumor activity and reduces animal toxicity and immunogenicity[J]. Proc Natl Acad Sci USA, 2000, 97(15):8548-8553.
[18]	BANGALORE S, KUMAR S, FUSARO M, et al. Outcomes with various drug eluting or bare metal stents in patients with diabetes mellitus:mixed treatment comparison analysis of 22844 patient years of follow-up from randomised trials[J]. BMJ, 2012, 345:e5170.
[19]	PASUT G, VERONESE FM. State of the art in PEGylation:The great versatility achieved after forty years of research[J]. J Control Release, 2012, 161(2):461-472.
[20]	MORGENSTERN J, BAUMANN P, BRUNNER C, et al. Effect of PEG molecular weight and PEGylation degree on the physical stability of PEGylated lysozyme[J]. Int J Pharm, 2017, 519(1-2):408-417.
[21]	ROBERTS MJ, HARRIS JM. Attachment of degradable poly(ethylene glycol) to proteins has the potential to increase therapeutic efficacy[J]. J Pharm Sci, 1998, 87(11):1440-1445.
[22]	ANDREW J. GARMAN S,BARRET KALINDJIAN. The preparation and properties of novel reversible polymer-protein conjugates 2-ω-Methoxypolyethylene (5000) glycoxymethylene-3-methylmaleyl conjugates of plasminogen activators[J]. Febs Lett, 1987, 223(2):361-365.
[23]	田浤, 金宇灏, 陈阳建,等. 聚乙二醇氨基酸衍生物的合成及其对紫杉醇的修饰[J]. 中国药科大学学报, 2011, 42(1):78-82.
[24]	KIZILEL S, SCAVONE A, LIU X, et al. Encapsulation of pancreatic islets within nano-thin functional polyethylene glycol coatings for enhanced insulin secretion[J]. Tissue Engin Part A, 2010, 16(7):2217.
[25]	YOO MK, PARK IK, LIM HT, et al. Folate PEG superparamagnetic iron oxide nanoparticles for lung cancer imaging[J]. Acta Biomater, 2012, 8(8):3005-3013.
[26]	ZHANG C, YANG XL, YUAN YH, et al. Site-specific PEGylation of therapeutic proteins via optimization of both accessible reactive amino acid residues and PEG derivatives[J]. Biodrugs, 2012, 26(4):209. 209-215.
[27]	RYAN SIN AD M, MANTOVANI GIUSEPPE, WANG XUEXUAN, et al. Advances in PEGylation of important biotech molecules:delivery aspects[J]. Expert Opin Drug Deliv,2008,5(4):371-383.
[28]	VUGMEYSTER Y,ENTRICAN C A,JOYCE AP,et al.Pharmacokinetic,biodistribution and biophysical profiles of TNF nanobodies conjugated to linear or branched poly (ethylene glycol)[J].Bioconjug Chem,2012,23(7):1452-1462.
[29]	DAVIS, FF.The origin of pegnology[J]. Adv Drug Deliv Rev,2002,54(4):457-458.
[30]	DAVIS FF, VAN EST, PALCZUK NC. Non-immunogenic polypeptides:US, US 4179337 A[P]. 1979.
[31]	ABUCHOWSKI A,MCCOY JR,PALCZUK NC,et al. Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase[J]. J Biol Chem,1977,252(11):3582-3586.
[32]	LEE CR,MCKENZIE CA,WEBSTER KD,et al. Pegademase bovine:replacement therapy for severe combined immunodeficiency disease[J]. DICP, 1991, 25(10):1092-1095
[33]	"Amgen 2016 Annual Report to Stockholders"[www.amgen.com/~/media/amgen/full/www-amgen-com/downloads/investors/2016-annual-report-letter-and-10k_restrict.ashx?la=en] 2016-annual-report-letter-and-10.pdf, 2017, p. 55
[34]	DE GRAAF AJ, KOOIJMAN M, HENNINK WE, et al. Nonnatural amino acids for site-specific protein conjugation[J]. Bioconjug Chem, 2009, 20(7):1281.
[35]	YANG BB, KIDO MA, MS MMS, et al. Pharmacokinetics and pharmacodynamics of pegfilgrastim in subjects with various degrees of renal function[J]. J Clin Pharmacol, 2011, 50(5):295-306.
[36]	TURECEK PL, BOSSARD MJ, GRANINGER M,et al. BAX 855, a PEGylated rFVⅢ product with prolonged half-life. Development, functional and structural characterisation[J]. Hamostaseologie, 2012, 32(Suppl 1):S29-S38.
[37]	WORLD HEALTH ORGANIZATION. WHO Guidelines on the Quality, Safety, and Efficacy of Biological Medicinal Products Prepared by Recombinant DNA Technology. Switzerland:WHO Press, 2013. 91-92.
[38]	LI XL, LIU L, GAO JP, et al. Methods for identification of conjugation site on PEGylated protein[J]. Pharmaceutical Biotechnology, 2013.
[39]	YU W, YU C, WU L, et al. PEGylated recombinant human interferon-ω as a long-acting antiviral agent:structure, antiviral activity and pharmacokinetics[J]. Antiviral Res, 2014, 108:142-147.
[40]	JOHN B, SWAPAN C, JOHNSTON D. Characterization of poly(ethylene glycol)-modified superoxide dismutase:Comparison of capillary electrophoresis and matrix-assisted laser desorption/ionization mass spectrometry[J]. Analytical Chemistry, 1996, 68(18):3258-3264.
[41]	李晶, 何辉, 程速远,等. 荧光胺衍生化法测定3种聚乙二醇化重组人生长激素的平均修饰率[J]. 药物分析杂志, 2014(8):1368-1373.

点击查看大图

计量

文章访问数: 6275
HTML全文浏览量: 594
PDF下载量: 1601
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

聚乙二醇衍生物及其蛋白药物修饰研究进展

doi: 10.3969/j.issn.1006-0111.2018.04.004

Advances in the development of PEG derivatives and pegylated protein drugs

计量

聚乙二醇衍生物及其蛋白药物修饰研究进展

doi: 10.3969/j.issn.1006-0111.2018.04.004

1. 中国药科大学, 江苏南京 210009;北京双鹭药业股份有限公司, 北京 100041

2. 北京双鹭药业股份有限公司, 北京 100041

3. 中国药科大学, 江苏南京 210009

English Abstract

Advances in the development of PEG derivatives and pegylated protein drugs

1. China Pharmaceutical University, Nanjing 210009, China;Beijing SL Pharmaceutical Co., Ltd., Beijing 100041, China

2. Beijing SL Pharmaceutical Co., Ltd., Beijing 100041, China

3. China Pharmaceutical University, Nanjing 210009, China

全文HTML

目录

[1]	宋雨桐, 夏德润, 顾珩, 唐少文, 易洪刚, 沃红梅. 帕博利珠单抗与铂类化疗方案在晚期非小细胞肺癌一线治疗中的药物经济学评价 . 药学实践与服务, 2024, 42(7): 1-7. doi: 10.12206/j.issn.2097-2024.202303023
[2]	张元林, 宋凯, 孙蕊, 舒飞, 舒丽芯, 杨樟卫. 基于真实世界数据的药物利用研究综述 . 药学实践与服务, 2024, 42(6): 238-243. doi: 10.12206/j.issn.2097-2024.202312010
[3]	陈炳辰, 佟达丰, 万苗, 闫飞虎, 姚建忠. UPLC-MS/MS法测定小鼠血浆中紫杉醇脂肪酸酯前药及其药代动力学研究 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202404082
[4]	景凯, 杨慈荣, 张圳, 臧艺蓓, 刘霞. 黄芪甲苷衍生物治疗慢性心力衰竭小鼠的药效评价及作用机制研究 . 药学实践与服务, 2024, 42(5): 190-197. doi: 10.12206/j.issn.2097-2024.202310004

留言板

聚乙二醇衍生物及其蛋白药物修饰研究进展

doi: 10.3969/j.issn.1006-0111.2018.04.004

Advances in the development of PEG derivatives and pegylated protein drugs

计量

出版历程

聚乙二醇衍生物及其蛋白药物修饰研究进展

doi: 10.3969/j.issn.1006-0111.2018.04.004

1. 中国药科大学, 江苏 南京 210009;北京双鹭药业股份有限公司, 北京 100041 2. 北京双鹭药业股份有限公司, 北京 100041 3. 中国药科大学, 江苏 南京 210009

English Abstract

Advances in the development of PEG derivatives and pegylated protein drugs

1. China Pharmaceutical University, Nanjing 210009, China;Beijing SL Pharmaceutical Co., Ltd., Beijing 100041, China 2. Beijing SL Pharmaceutical Co., Ltd., Beijing 100041, China 3. China Pharmaceutical University, Nanjing 210009, China

全文HTML

目录

1. 中国药科大学, 江苏南京 210009;北京双鹭药业股份有限公司, 北京 100041

2. 北京双鹭药业股份有限公司, 北京 100041

3. 中国药科大学, 江苏南京 210009

1. China Pharmaceutical University, Nanjing 210009, China;Beijing SL Pharmaceutical Co., Ltd., Beijing 100041, China

2. Beijing SL Pharmaceutical Co., Ltd., Beijing 100041, China

3. China Pharmaceutical University, Nanjing 210009, China