{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T07:30:05Z","timestamp":1793604605184,"version":"4.5.0"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570537"],"award-info":[{"award-number":["81570537"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974074"],"award-info":[{"award-number":["81974074"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172654"],"award-info":[{"award-number":["82172654"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002767","name":"Hunan Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["2018RS3026"],"award-info":[{"award-number":["2018RS3026"]}],"id":[{"id":"10.13039\/501100002767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002767","name":"Hunan Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["2021RC4012"],"award-info":[{"award-number":["2021RC4012"]}],"id":[{"id":"10.13039\/501100002767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Hunan Provincial Natural Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2022,11]]},"DOI":"10.1016\/j.ejmech.2022.114672","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T14:36:53Z","timestamp":1660142213000},"page":"114672","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Site-specific N-terminal PEGylation-based controlled release of biotherapeutics: An application for GLP-1 delivery to improve pharmacokinetics and prolong hypoglycemic effects"],"prefix":"10.1016","volume":"242","author":[{"given":"Qianmeng","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2022.114672_bib1","doi-asserted-by":"crossref","first-page":"14323","DOI":"10.1021\/ja504390x","article-title":"Therapeutic protein-polymer conjugates: advancing beyond PEGylation","volume":"136","author":"Pelegri-O'Day","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2022.114672_bib2","doi-asserted-by":"crossref","first-page":"10995","DOI":"10.1021\/jacs.6b05413","article-title":"A concise approach to site-specific topological protein-poly(amino acid) conjugates enabled by in situ-generated functionalities","volume":"138","author":"Hou","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2022.114672_bib3","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3390\/polym6010160","article-title":"Polymers for protein conjugation","volume":"6","author":"Pasut","year":"2014","journal-title":"Polymers"},{"key":"10.1016\/j.ejmech.2022.114672_bib4","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jddst.2015.08.006","article-title":"Drug and protein delivery by polymer conjugation","volume":"32","author":"Grigoletto","year":"2016","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"10.1016\/j.ejmech.2022.114672_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.carbpol.2020.116864","article-title":"Site-selective modification of exendin 4 with variable molecular weight dextrans by oxime-ligation chemistry for improving type 2 diabetic treatment","volume":"249","author":"Dai","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"10.1016\/j.ejmech.2022.114672_bib6","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.addr.2009.02.010","article-title":"PEG conjugates in clinical development or use as anticancer agents: an overview","volume":"61","author":"Pasut","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejmech.2022.114672_bib7","doi-asserted-by":"crossref","first-page":"25831","DOI":"10.3390\/ijms161025831","article-title":"Site-specific PEGylation of therapeutic proteins","volume":"16","author":"Dozier","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2022.114672_bib8","doi-asserted-by":"crossref","first-page":"5307","DOI":"10.1002\/anie.200600368","article-title":"N-terminal protein modification through a biomimetic transamination reaction","volume":"45","author":"Gilmore","year":"2006","journal-title":"Angew Chem. Int. Ed. Engl."},{"key":"10.1016\/j.ejmech.2022.114672_bib9","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1021\/ja208009r","article-title":"Modification of N-terminal alpha-amino groups of peptides and proteins using ketenes","volume":"134","author":"Chan","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2022.114672_bib10","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.jconrel.2011.10.037","article-title":"State of the art in PEGylation: the great versatility achieved after forty years of research","volume":"161","author":"Pasut","year":"2012","journal-title":"J. Contr. Release : official journal of the Controlled Release Society"},{"key":"10.1016\/j.ejmech.2022.114672_bib11","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1002\/jps.22103","article-title":"Purification of PEGylated protein using membrane chromatography","volume":"99","author":"Yu","year":"2010","journal-title":"J. Pharmaceut. Sci."},{"key":"10.1016\/j.ejmech.2022.114672_bib12","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/nchembio.2416","article-title":"Targeting the N terminus for site-selective protein modification","volume":"13","author":"Rosen","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ejmech.2022.114672_bib13","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1021\/bc950074d","article-title":"Site-specific attachment of functionalized poly(ethylene glycol) to the amino terminus of proteins","volume":"7","author":"Gaertner","year":"1996","journal-title":"Bioconjugate Chem."},{"key":"10.1016\/j.ejmech.2022.114672_bib14","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1021\/bc400435u","article-title":"Comparison of site-specific PEGylations of the N-terminus of interferon beta-1b: selectivity, efficiency, and in vivo\/vitro activity","volume":"25","author":"Zhou","year":"2014","journal-title":"Bioconjugate Chem."},{"key":"10.1016\/j.ejmech.2022.114672_bib15","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1021\/jm500810s","article-title":"Glucagon-like peptide-1 (GLP-1) analogs: recent advances, new possibilities, and therapeutic implications","volume":"58","author":"Manandhar","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114672_bib16","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ejps.2006.01.003","article-title":"GLP-1 based therapy for type 2 diabetes","volume":"28","author":"Arulmozhi","year":"2006","journal-title":"Eur. J. Pharmaceut. Sci."},{"key":"10.1016\/j.ejmech.2022.114672_bib17","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.toxicon.2010.12.016","article-title":"The development of Byetta (exenatide) from the venom of the Gila monster as an anti-diabetic agent","volume":"59","author":"Furman","year":"2012","journal-title":"Toxicon"},{"key":"10.1016\/j.ejmech.2022.114672_bib18","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1517\/13543784.8.9.1409","article-title":"Treatment of Type 2 diabetes mellitus based on glucagon-like peptide-1","volume":"8","author":"Holst","year":"1999","journal-title":"Expet Opin. Invest. Drugs"},{"key":"10.1016\/j.ejmech.2022.114672_bib19","doi-asserted-by":"crossref","first-page":"12848","DOI":"10.1021\/ja507168t","article-title":"A potent alpha\/beta-peptide analogue of GLP-1 with prolonged action in vivo","volume":"136","author":"Johnson","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2022.114672_bib20","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/cmdc.201700781","article-title":"Glucagon-like peptide-1 (GLP-1)-Based therapeutics: current status and future opportunities beyond type 2 diabetes","volume":"13","author":"Cheang","year":"2018","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2022.114672_bib21","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.addr.2018.07.009","article-title":"Battle of GLP-1 delivery technologies","volume":"130","author":"Yu","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejmech.2022.114672_bib22","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1021\/bc049735+","article-title":"Synthesis, characterization, and pharmacokinetic studies of PEGylated glucagon-like peptide-1","volume":"16","author":"Lee","year":"2005","journal-title":"Bioconjugate Chem."},{"key":"10.1016\/j.ejmech.2022.114672_bib23","doi-asserted-by":"crossref","first-page":"5252","DOI":"10.1111\/bph.12843","article-title":"Novel coumarin modified GLP-1 derivatives with enhanced plasma stability and prolonged in vivo glucose-lowering ability","volume":"171","author":"Han","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2022.114672_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112496","article-title":"A novel long-acting oxyntomodulin analogue eliminates diabetes and obesity in mice","volume":"203","author":"Ma","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114672_bib25","article-title":"The ARRIVE guidelines 2.0: updated guidelines for reporting animal research","volume":"18","author":"Percie du Sert","year":"2020","journal-title":"PLoS Biol."},{"key":"10.1016\/j.ejmech.2022.114672_bib26","doi-asserted-by":"crossref","DOI":"10.1038\/s41551-017-0078","article-title":"One-week glucose control via zero-order release kinetics from an injectable depot of glucagon-like peptide-1 fused to a thermosensitive biopolymer","volume":"1","author":"Luginbuhl","year":"2017","journal-title":"Nature biomedical engineering"},{"key":"10.1016\/j.ejmech.2022.114672_bib27","doi-asserted-by":"crossref","first-page":"6275","DOI":"10.1016\/S0021-9258(17)37366-0","article-title":"Structure-activity studies of glucagon-like peptide-1","volume":"269","author":"Adelhorst","year":"1994","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejmech.2022.114672_bib28","doi-asserted-by":"crossref","first-page":"19650","DOI":"10.1016\/S0021-9258(19)36565-2","article-title":"Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells","volume":"268","author":"Goke","year":"1993","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejmech.2022.114672_bib29","doi-asserted-by":"crossref","first-page":"6275","DOI":"10.1016\/S0021-9258(17)37366-0","article-title":"Structure-activity studies of glucagon-like peptide-1","volume":"269","author":"Adelhorst","year":"1994","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejmech.2022.114672_bib30","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1021\/bc000082g","article-title":"Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon alpha-2a for the treatment of hepatitis C","volume":"12","author":"Bailon","year":"2001","journal-title":"Bioconjugate Chem."},{"key":"10.1016\/j.ejmech.2022.114672_bib31","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0304-4165(99)00214-7","article-title":"N-terminally modified glucagon-like peptide-1(7-36) amide exhibits resistance to enzymatic degradation while maintaining its antihyperglycaemic activity in vivo","volume":"1474","author":"O'Harte","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ejmech.2022.114672_bib32","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1124\/pr.115.011395","article-title":"Glucagon-like peptide-1 and its class B G protein-coupled receptors: a long march to therapeutic successes","volume":"68","author":"Graaf","year":"2016","journal-title":"Pharmacol. Rev."},{"issue":"Pt 1","key":"10.1016\/j.ejmech.2022.114672_bib33","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1042\/bj3100203","article-title":"Agonist-induced internalization and recycling of the glucagon-like peptide-1 receptor in transfected fibroblasts and in insulinomas","volume":"310","author":"Widmann","year":"1995","journal-title":"Biochem. J."},{"key":"10.1016\/j.ejmech.2022.114672_bib34","doi-asserted-by":"crossref","first-page":"E161","DOI":"10.1152\/ajpendo.00551.2012","article-title":"Glucagon-like peptide-1 receptor-mediated endosomal cAMP generation promotes glucose-stimulated insulin secretion in pancreatic beta-cells","volume":"305","author":"Kuna","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.ejmech.2022.114672_bib35","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0021-9258(18)54155-7","article-title":"Beta-adrenergic receptor sequestration. A potential mechanism of receptor resensitization","volume":"268","author":"Yu","year":"1993","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejmech.2022.114672_bib36","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1038\/s41467-018-03941-2","article-title":"Targeting GLP-1 receptor trafficking to improve agonist efficacy","volume":"9","author":"Jones","year":"2018","journal-title":"Nat. Commun."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523422005748?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523422005748?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:41:24Z","timestamp":1759329684000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523422005748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":36,"alternative-id":["S0223523422005748"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2022.114672","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2022,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Site-specific N-terminal PEGylation-based controlled release of biotherapeutics: An application for GLP-1 delivery to improve pharmacokinetics and prolong hypoglycemic effects","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2022.114672","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"114672"}}