{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:23:48Z","timestamp":1789129428851,"version":"build-2803163510"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"European Research Council"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-024-54076-6","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T07:03:41Z","timestamp":1731481421000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Exactly defined molecular weight poly(ethylene glycol) allows for facile identification of PEGylation sites on proteins"],"prefix":"10.1038","volume":"15","author":[{"given":"Maria J.","family":"Burggraef","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2100-7183","authenticated-orcid":false,"given":"Adam","family":"Oxley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveed A.","family":"Zaidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3426-2274","authenticated-orcid":false,"given":"Pedro R.","family":"Cutillas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piers R. J.","family":"Gaffney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7916-3026","authenticated-orcid":false,"given":"Andrew G.","family":"Livingston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"54076_CR1","doi-asserted-by":"publisher","first-page":"3578","DOI":"10.1016\/S0021-9258(17)40291-2","volume":"252","author":"A Abuchowski","year":"1977","unstructured":"Abuchowski, A., van Es, T., Palczuk, N. C. & Davis, F. F. Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. J. Biol. Chem. 252, 3578\u20133581 (1977).","journal-title":"J. Biol. Chem."},{"key":"54076_CR2","unstructured":"Srichana, T. & Suwandecha, T. Biodegradable Polymers in Clinical Use and Clinical Development (John Wiley & Sons, Inc., 2011)."},{"key":"54076_CR3","doi-asserted-by":"crossref","unstructured":"Zalipsky, S. & Harris, J. M. Introduction to Chemistry and Biological Applications of Poly(ethylene glycol). (American Chemical Society, 1997).","DOI":"10.1021\/bk-1997-0680.ch001"},{"key":"54076_CR4","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/S0169-409X(02)00022-4","volume":"54","author":"MJ Roberts","year":"2002","unstructured":"Roberts, M. J., Bentley, M. D. & Harris, J. M. Chemistry for peptide and protein PEGylation. Adv. Drug Deliv. Rev. 54, 459\u2013476 (2002).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"54076_CR5","doi-asserted-by":"publisher","first-page":"6288","DOI":"10.1002\/anie.200902672","volume":"49","author":"K Knop","year":"2010","unstructured":"Knop, K., Hoogenboom, R., Fischer, D. & Schubert, U. S. Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew. Chem. Int. Ed. Engl. 49, 6288\u20136308 (2010).","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"54076_CR6","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1080\/17425247.2016.1182485","volume":"13","author":"AA D\u2019souza","year":"2016","unstructured":"D\u2019souza, A. A. & Shegokar, R. Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications. Expert Opin. Drug Deliv. 13, 1257\u20131275 (2016).","journal-title":"Expert Opin. Drug Deliv."},{"key":"54076_CR7","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/nrd1033","volume":"2","author":"JM Harris","year":"2003","unstructured":"Harris, J. M. & Chess, R. B. Effect of pegylation on pharmaceuticals. Nat. Rev. Drug Discov. 2, 214\u2013221 (2003).","journal-title":"Nat. Rev. Drug Discov."},{"key":"54076_CR8","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/S0142-9612(00)00193-9","volume":"22","author":"FM Veronese","year":"2001","unstructured":"Veronese, F. M. Peptide and protein PEGylation: a review of problems and solutions. Biomaterials 22, 405\u2013417 (2001).","journal-title":"Biomaterials"},{"key":"54076_CR9","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1517\/14728214.2015.1113254","volume":"20","author":"M Swierczewska","year":"2015","unstructured":"Swierczewska, M., Lee, K. C. & Lee, S. What is the future of PEGylated therapies? Expert Opin. Emerg. Drugs 20, 531\u2013536 (2015).","journal-title":"Expert Opin. Emerg. Drugs"},{"key":"54076_CR10","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.xphs.2015.11.015","volume":"105","author":"PL Turecek","year":"2016","unstructured":"Turecek, P. L., Bossard, M. J., Schoetens, F. & Ivens, I. A. PEGylation of biopharmaceuticals: a review of chemistry and nonclinical safety information of approved drugs. J. Pharm. Sci. 105, 460\u2013475 (2016).","journal-title":"J. Pharm. Sci."},{"key":"54076_CR11","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1016\/S1359-6446(05)03575-0","volume":"10","author":"FM Veronese","year":"2005","unstructured":"Veronese, F. M. & Pasut, G. PEGylation, successful approach to drug delivery. Drug Discov. Today 10, 1451\u20131458 (2005).","journal-title":"Drug Discov. Today"},{"key":"54076_CR12","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/s12079-018-0492-0","volume":"13","author":"V Gupta","year":"2019","unstructured":"Gupta, V. et al. Protein PEGylation for cancer therapy: bench to bedside. J. Cell Commun. Signal 13, 319\u2013330 (2019).","journal-title":"J. Cell Commun. Signal"},{"key":"54076_CR13","doi-asserted-by":"publisher","first-page":"10848","DOI":"10.1021\/acs.analchem.6b03577","volume":"88","author":"EJ Park","year":"2016","unstructured":"Park, E. J. & Na, D. H. Characterization of the reversed-phase chromatographic behavior of PEGylated peptides based on the Poly(ethylene glycol) dispersity. Anal. Chem. 88, 10848\u201310853 (2016).","journal-title":"Anal. Chem."},{"key":"54076_CR14","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1006\/abio.1997.2128","volume":"247","author":"SP Monkarsh","year":"1997","unstructured":"Monkarsh, S. P. et al. Positional isomers of monopegylated interferon \u03b1-2a: isolation, characterization, and biological activity. Anal. Biochem. 247, 434\u2013440 (1997).","journal-title":"Anal. Biochem."},{"key":"54076_CR15","unstructured":"Kirwan, P. Product Quality Review(s) 761075Orig1s000. 92-153 (U.S. Food & Drug Administration, 2018)."},{"key":"54076_CR16","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.aca.2017.12.009","volume":"1004","author":"S Gerislioglu","year":"2018","unstructured":"Gerislioglu, S., Adams, S. R. & Wesdemiotis, C. Characterization of singly and multiply PEGylated insulin isomers by reversed-phase ultra-performance liquid chromatography interfaced with ion mobility mass spectrometry. Anal. Chim. Acta 1004, 58\u201366 (2018).","journal-title":"Anal. Chim. Acta"},{"key":"54076_CR17","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.ijpharm.2013.06.059","volume":"454","author":"X Qian","year":"2013","unstructured":"Qian, X. et al. Characterization of a site-specific PEGylated analog of exendin-4 and determination of the PEGylation site. Int. J. Pharm. 454, 553\u2013558 (2013).","journal-title":"Int. J. Pharm."},{"key":"54076_CR18","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1016\/S0169-409X(03)00108-X","volume":"55","author":"P Caliceti","year":"2003","unstructured":"Caliceti, P. & Veronese, F. M. Pharmacokinetic and biodistribution properties of poly(ethylene glycol)\u2013protein conjugates. Adv. Drug Deliv. Rev. 55, 1261\u20131277 (2003).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"54076_CR19","doi-asserted-by":"publisher","first-page":"2170","DOI":"10.1021\/acs.chemrev.5b00441","volume":"116","author":"J Herzberger","year":"2016","unstructured":"Herzberger, J. et al. Polymerization of ethylene oxide, propylene oxide, and other alkylene oxides: synthesis, novel polymer architectures, and bioconjugation. Chem. Rev. 116, 2170\u20132243 (2016).","journal-title":"Chem. Rev."},{"key":"54076_CR20","unstructured":"Agner, E. Method for displacement chromatography. United States patent US 6,576,134 B1 (2003)."},{"key":"54076_CR21","unstructured":"Agner, E. Purification of Peptides and Oligonucleotides by Sample Displacement Chromatography process and apparatus. United States patent US 6,245,238 B1 (1999)."},{"key":"54076_CR22","unstructured":"Polypure A. S. mPEG-45 (Catalogue Number 1011-4595), https:\/\/polypure.com\/products\/peg\/peg-28 (2024)."},{"key":"54076_CR23","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1139\/cjr36b-011","volume":"14b","author":"SZ Perry","year":"1936","unstructured":"Perry, S. Z. & Hibbert, H. Studies on reactions relating to carbohydrates and polysaccharides: XLVIII. Ethylene Oxide and related compounds: synthesis of the polyethylene glycols. Can. J. Res. 14b, 77\u201383 (1936).","journal-title":"Can. J. Res."},{"key":"54076_CR24","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1021\/ja01876a072","volume":"61","author":"R Fordyce","year":"1939","unstructured":"Fordyce, R., Lovell, E. L. & Hibbert, H. Studies on reactions relating to carbohydrates and polysaccharides. LVI. The synthesis of the higher polyoxyethylene glycols. J. Am. Chem. Soc. 61, 1905\u20131910 (1939).","journal-title":"J. Am. Chem. Soc."},{"key":"54076_CR25","doi-asserted-by":"publisher","first-page":"6678","DOI":"10.1021\/jo00050a065","volume":"57","author":"EMD Keegstra","year":"1992","unstructured":"Keegstra, E. M. D., Zwikker, J. W., Roest, M. R. & Jenneskens, L. W. A highly selective synthesis of monodisperse oligo(ethylene glycols). J. Org. Chem. 57, 6678\u20136680 (1992).","journal-title":"J. Org. Chem."},{"key":"54076_CR26","doi-asserted-by":"publisher","first-page":"3192","DOI":"10.1021\/ja00087a004","volume":"116","author":"A Harada","year":"1994","unstructured":"Harada, A., Li, J. & Kamachi, M. Preparation and characterization of a polyrotaxane consisting of monodisperse Poly(ethylene glycol) and.alpha.-Cyclodextrins. J. Am. Chem. Soc. 116, 3192\u20133196 (1994).","journal-title":"J. Am. Chem. Soc."},{"key":"54076_CR27","doi-asserted-by":"publisher","first-page":"9884","DOI":"10.1021\/jo0617464","volume":"71","author":"SA Ahmed","year":"2006","unstructured":"Ahmed, S. A. & Tanaka, M. Synthesis of Oligo(ethylene glycol) toward 44-mer. J. Org. Chem. 71, 9884\u20139886 (2006).","journal-title":"J. Org. Chem."},{"key":"54076_CR28","doi-asserted-by":"publisher","first-page":"6411","DOI":"10.1002\/anie.201403436","volume":"53","author":"K Maranski","year":"2014","unstructured":"Maranski, K., Andreev, Y. G. & Bruce, P. G. Synthesis of poly(ethylene oxide) approaching monodispersity. Angew. Chem. Int. Ed. 53, 6411\u20136413 (2014).","journal-title":"Angew. Chem. Int. Ed."},{"key":"54076_CR29","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/s41428-019-0277-1","volume":"52","author":"P Bohn","year":"2020","unstructured":"Bohn, P. & Meier, M. A. R. Uniform poly(ethylene glycol): a comparative study. Polym. J. 52, 165\u2013178 (2020).","journal-title":"Polym. J."},{"key":"54076_CR30","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1002\/anie.200804623","volume":"48","author":"AC French","year":"2009","unstructured":"French, A. C., Thompson, A. L. & Davis, B. G. High-purity discrete PEG-oligomer crystals allow structural insight. Angew. Chem. Int. Ed. 48, 1248\u20131252 (2009).","journal-title":"Angew. Chem. Int. Ed."},{"key":"54076_CR31","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1021\/jo035042v","volume":"69","author":"FA Loiseau","year":"2004","unstructured":"Loiseau, F. A., Hii, K. K. & Hill, A. M. Multigram synthesis of well-defined extended bifunctional polyethylene glycol (PEG) chains. J. Org. Chem. 69, 639\u2013647 (2004).","journal-title":"J. Org. Chem."},{"key":"54076_CR32","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1021\/bc060242+","volume":"19","author":"D Niculescu-Duvaz","year":"2008","unstructured":"Niculescu-Duvaz, D., Getaz, J. & Springer, C. J. Long functionalized poly(ethylene glycol)s of defined molecular weight: synthesis and application in solid-phase synthesis of conjugates. Bioconjug. Chem. 19, 973\u2013981 (2008).","journal-title":"Bioconjug. Chem."},{"key":"54076_CR33","doi-asserted-by":"publisher","first-page":"10038","DOI":"10.1002\/chem.201402186","volume":"20","author":"G Szekely","year":"2014","unstructured":"Szekely, G., Schaepertoens, M., Gaffney, P. R. & Livingston, A. G. Beyond PEG2000: synthesis and functionalisation of monodisperse PEGylated homostars and clickable bivalent polyethyleneglycols. Chem. Eur. J. 20, 10038\u201310051 (2014).","journal-title":"Chem. Eur. J."},{"key":"54076_CR34","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1039\/C3PY01367G","volume":"5","author":"G Sz\u00e9kely","year":"2014","unstructured":"Sz\u00e9kely, G., Schaepertoens, M., Gaffney, P. R. J. & Livingston, A. G. Iterative synthesis of monodisperse PEG homostars and linear heterobifunctional PEG. Polym. Chem. 5, 694\u2013697 (2014).","journal-title":"Polym. Chem."},{"key":"54076_CR35","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1016\/j.tetlet.2014.02.047","volume":"55","author":"Y Li","year":"2014","unstructured":"Li, Y. et al. Fluorous synthesis of mono-dispersed poly(ethylene glycols). Tetrahedron Lett. 55, 2110\u20132113 (2014).","journal-title":"Tetrahedron Lett."},{"key":"54076_CR36","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1021\/acs.oprd.5b00142","volume":"19","author":"Y Li","year":"2015","unstructured":"Li, Y., Qiu, X. & Jiang, Z.-X. Macrocyclic sulfates as versatile building blocks in the synthesis of monodisperse poly(ethylene glycol)s and monofunctionalized derivatives. Org. Process Res. Dev. 19, 800\u2013805 (2015).","journal-title":"Org. Process Res. Dev."},{"key":"54076_CR37","doi-asserted-by":"publisher","first-page":"3763","DOI":"10.1002\/anie.201410309","volume":"54","author":"H Zhang","year":"2015","unstructured":"Zhang, H. et al. Highly efficient synthesis of monodisperse poly(ethylene glycols) and derivatives through macrocyclization of oligo(ethylene glycols). Angew. Chem. Int. Ed. 54, 3763\u20133767 (2015).","journal-title":"Angew. Chem. Int. Ed."},{"key":"54076_CR38","doi-asserted-by":"publisher","first-page":"3384","DOI":"10.1016\/j.tetlet.2014.04.066","volume":"55","author":"Q Zhang","year":"2014","unstructured":"Zhang, Q., Ren, H. & Baker, G. L. A practical and scalable process to selectively monofunctionalize water-soluble \u03b1,\u03c9-diols. Tetrahedron Lett. 55, 3384\u20133386 (2014).","journal-title":"Tetrahedron Lett."},{"key":"54076_CR39","doi-asserted-by":"crossref","unstructured":"Wawro, A., Muraoka, T. & Kinbara, K. Chromatography-free synthesis of monodisperse oligo(ethylene glycol) mono-p-toluenesulfonates and quantitative analysis of oligomer purity. Polym. Chem. 7, 2389\u20132394 (2016).","DOI":"10.1039\/C6PY00127K"},{"key":"54076_CR40","doi-asserted-by":"publisher","first-page":"15133","DOI":"10.1002\/chem.201703004","volume":"23","author":"A Khanal","year":"2017","unstructured":"Khanal, A. & Fang, S. Solid phase stepwise synthesis of polyethylene glycols. Chem. Eur. J. 23, 15133\u201315142 (2017).","journal-title":"Chem. Eur. J."},{"key":"54076_CR41","doi-asserted-by":"publisher","first-page":"132861","DOI":"10.1016\/j.tet.2022.132861","volume":"119","author":"DNAM Eriyagama","year":"2022","unstructured":"Eriyagama, D. N. A. M., Yin, Y. & Fang, S. Automated stepwise PEG synthesis using a base-labile protecting group. Tetrahedron 119, 132861 (2022).","journal-title":"Tetrahedron"},{"key":"54076_CR42","doi-asserted-by":"crossref","unstructured":"Dong, R. et al. Sequence-defined multifunctional polyethers via liquid-phase synthesis with molecular sieving. Nat. Chem. 11, 136\u2013145 (2019).","DOI":"10.1038\/s41557-018-0169-6"},{"key":"54076_CR43","doi-asserted-by":"publisher","first-page":"7786","DOI":"10.1002\/anie.202014445","volume":"60","author":"J Yeo","year":"2021","unstructured":"Yeo, J. et al. Liquid phase peptide synthesis via one-pot nanostar sieving (PEPSTAR). Angew. Chem. Int. Ed. 60, 7786\u20137795 (2021).","journal-title":"Angew. Chem. Int. Ed."},{"key":"54076_CR44","doi-asserted-by":"publisher","first-page":"3134","DOI":"10.1021\/acs.biomac.0c00517","volume":"21","author":"J Wang","year":"2020","unstructured":"Wang, J. et al. Monodisperse and polydisperse PEGylation of peptides and proteins: a comparative study. Biomacromolecules 21, 3134\u20133139 (2020).","journal-title":"Biomacromolecules"},{"key":"54076_CR45","doi-asserted-by":"publisher","first-page":"120977","DOI":"10.1016\/j.memsci.2022.120977","volume":"662","author":"A Oxley","year":"2022","unstructured":"Oxley, A. & Livingston, A. G. Anti-fouling membranes for organic solvent nanofiltration (OSN) and organic solvent ultrafiltration (OSU): graft modified polybenzimidazole (PBI). J. Membr. Sci. 662, 120977 (2022).","journal-title":"J. Membr. Sci."},{"key":"54076_CR46","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1039\/C3GC41402G","volume":"16","author":"JF Kim","year":"2014","unstructured":"Kim, J. F., Sz\u00e9kely, G., Valtcheva, I. B. & Livingston, A. G. Increasing the sustainability of membrane processes through cascade approach and solvent recovery\u2014pharmaceutical purification case study. Green. Chem. 16, 133\u2013145 (2014).","journal-title":"Green. Chem."},{"key":"54076_CR47","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1021\/bc049843w","volume":"15","author":"CJ Fee","year":"2004","unstructured":"Fee, C. J. & Van Alstine, J. M. Prediction of the viscosity radius and the size exclusion chromatography behavior of PEGylated proteins. Bioconjug. Chem. 15, 1304\u20131313 (2004).","journal-title":"Bioconjug. Chem."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-54076-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-54076-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-54076-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T07:07:41Z","timestamp":1731481661000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-54076-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,13]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["54076"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-54076-6","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,13]]},"assertion":[{"value":"16 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Queen Mary University of London has filed a UK patent application (no. 2402623.9) related to defined molecular weight PEGylation agents. A.G.L. and M.J.B. are listed as inventors. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"9814"}}