{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:54:40Z","timestamp":1792173280064,"version":"4.4.0"},"reference-count":73,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T00:00:00Z","timestamp":1660348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201707040053"],"award-info":[{"award-number":["201707040053"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Conjugation to polyethylene glycol (PEG) is a widely used approach to improve the therapeutic value of proteins essentially by prolonging their body residence time. PEGylation may however induce changes in the structure and\/or the stability of proteins and thus on their function(s). The effects of PEGylation on the thermodynamic stability can either be positive (stabilization), negative (destabilization), or neutral (no effect). Moreover, various factors such as the PEG length and PEGylation site can influence the consequences of PEGylation on the structure and stability of proteins. In this study, the effects of PEGylation on the structure, stability, and polymerization of alpha1\u2010antitrypsin (AAT) were investigated, using PEGs with different lengths, different structures (linear or 2\u2010armed) and different linking chemistries (via amine or thiol) at two distinct positions of the sequence. The results show that whatever the size, position, and structure of PEG chains, PEGylation (a) does not induce significant changes in AAT structure (either at the secondary or tertiary level); (b) does not alter the stability of the native protein upon both chemical\u2010 and heat\u2010induced denaturation; and (c) does not prevent AAT to fully refold and recover its activity following chemical denaturation. However, the propensity of AAT to aggregate upon heat treatment was significantly decreased by PEGylation, although PEGylation did not prevent the irreversible inactivation of the enzyme. Moreover, conjugation to PEG, especially 2\u2010armed 40 kDa PEG, greatly improved the proteolytic resistance of AAT. PEGylation of AAT could be a promising strategy to prolong its half\u2010life after infusion in AAT\u2010deficient patients and thereby decrease the frequency of infusions.<\/jats:p>","DOI":"10.1002\/pro.4392","type":"journal-article","created":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T12:01:18Z","timestamp":1660392078000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Impact of the PEG length and PEGylation site on the structural, thermodynamic, thermal, and proteolytic stability of mono\u2010PEGylated alpha\u20101 antitrypsin"],"prefix":"10.1002","volume":"31","author":[{"given":"Xiao","family":"Liu","sequence":"first","affiliation":[{"name":"Advanced Drug Delivery and Biomaterials Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain (UCLouvain)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kobenan G. W.","family":"Kouassi","sequence":"additional","affiliation":[{"name":"Advanced Drug Delivery and Biomaterials Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain (UCLouvain)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0784-8771","authenticated-orcid":false,"given":"Rita","family":"Vanbever","sequence":"additional","affiliation":[{"name":"Advanced Drug Delivery and Biomaterials Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain (UCLouvain)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille","family":"Dumoulin","sequence":"additional","affiliation":[{"name":"Department of Life Sciences InBios, Center for Protein Engineering, Nanobodies to Explore Protein Structure and Functions, University of Li\u00e8ge  Li\u00e8ge Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S149429"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.5.3329"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2002-0258OC"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/139.3.783"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753465810373911"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00673-2019"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2011.10.037"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2015.11.015"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202101633"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(05)03575-0"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2013.06.022"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.2165\/00063030-200822050-00004"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2016.08.006"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1695"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm2005017"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb200277u"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.22014"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc025561p"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2011.05.003"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.2011.01288.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm800113g"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja5095183"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.09.013"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200900140"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.5104"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036612"},{"issue":"2","key":"e_1_2_8_28_1","first-page":"8","article-title":"Construction of an engineered alpha 1\u2010antitrypsin with inhibitory activity based on theoretical studies","volume":"15","author":"Dasi Sangachini E","year":"2012","journal-title":"Electron J Biotechnol"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2007.01.002"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00341"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2005.051979"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00512"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.121355"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.4866"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm1006954"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2017.03.057"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2010.12.034"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2006.01004.x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2019.05.038"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6PY01616B"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2010.12.030"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-009-9986-4"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.12515"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.05.039"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1976"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.11.048"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311731200"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2000.2186"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2018.10.045"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.1458"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1513\/pats.201004-031AW"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109125109"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.08.105"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42987"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm070687z"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00608.x"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4165(96)00143-2"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00053a014"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2015-0154OC"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp500658w"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.052004006"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc070123"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.129.6.1683"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.10.5282"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203832200"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201400115"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.1689"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc3002248"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2011.163006"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(86)31045-0"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi100369d"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.11.046"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90221-1"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(78)90286-2"}],"container-title":["Protein Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.4392","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pro.4392","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.4392","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T14:39:05Z","timestamp":1692715145000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pro.4392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,13]]},"references-count":73,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1002\/pro.4392"],"URL":"https:\/\/doi.org\/10.1002\/pro.4392","archive":["Portico"],"relation":{},"ISSN":["0961-8368","1469-896X"],"issn-type":[{"value":"0961-8368","type":"print"},{"value":"1469-896X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,13]]},"assertion":[{"value":"2022-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e4392"}}