{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:13:40Z","timestamp":1788232420423,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006396","name":"Qazvin University of Medical Sciences","doi-asserted-by":"publisher","award":["402000043"],"award-info":[{"award-number":["402000043"]}],"id":[{"id":"10.13039\/501100006396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech and App Biochem"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Streptokinase (SK) is an enzyme drug and is used in medicine for dissolving clots in conditions such as heart attacks, lung artery emboli, vein thrombosis, and occlusions of arteries. Despite the impressive use of SK, its immunogenicity and short half\u2010life are major challenges that limit its efficacy in clinical settings. In this communication, we studied the polysialylation of SK with the aim of improving the pharmacokinetics of this thrombolytic drug. Recombinant SK was covalently conjugated to polysialic acid (PSA; also referred to as colominic acid [CA]) via reductive amination. Native and polysialylated variants were compared in terms of structural properties, enzyme kinetics, stability, immunization, and biological half\u2010life. The best molecular weight of PSA, optimum molar ratio, incubation time, and temperature for the conjugation reaction were determined to be 10.0\u00a0kDa, 200:1, 24\u00a0h, and 25\u00b0C, respectively. The exact molecular weight of SK\u201010.0\u00a0kDa PSA was determined to be 56.5\u00a0kDa by MALDI\u2010TOF mass spectrometry, which matches the calculated value by SDS\u2010PAGE. The intrinsic fluorescence intensity of polysialylated SK increased compared to the native version, meaning that the stability of SK was increased by immobilization on the PSA polymer.\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>m<\/jats:sub>\n                    of polysialylated SK was slightly higher than that of native SK, which showed that the attached PSA molecules to the enzyme did not significantly reduce the substrate specificity. Polysialylated SK elicited nearly 63.0% lower antibody production compared to the native variant. Native and polysialylated SKs exhibited plasma half\u2010lives of 0.5 and 2.21\u00a0h, respectively, implying that the modified variant has a 4.42\u2010fold longer residence time in the body. Briefly, comparative studies with native and PSA\u2010conjugated enzymes show that polysialylation can be useful in enhancing the therapeutic efficacy of SK. It is worth emphasizing that this is the first report describing the use of polysialylation technology to improve the pharmaceutical properties of SK.\n                  <\/jats:p>","DOI":"10.1002\/bab.70194","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T02:37:36Z","timestamp":1788230256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Analysis of Biochemical and Pharmaceutical Properties of Polysialylated Recombinant Streptokinase Enzyme"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2099-1812","authenticated-orcid":false,"given":"Hamid","family":"Shahbazmohammadi","sequence":"first","affiliation":[{"name":"Cellular and Molecular Research Center, Research Institute for Prevention of Non\u2010Communicable Diseases Qazvin University of Medical Sciences  Qazvin Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eskandar","family":"Omidinia","sequence":"additional","affiliation":[{"name":"Enzyme Technology Laboratory, Department of Biochemistry Genetic and Metabolism Research Group, Pasteur Institute of Iran  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ihj.2021.02.005"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2021.03.021"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14787"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.016262"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.jvca.2019.05.035"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2022.103799"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.genrep.2022.101689"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2016.08.003"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2021.06.806"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016\u20105085(21)01415\u20103"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2021.05.028"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2019.11.157"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2020.111427"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0155831"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2021.06.809"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2016.1229718"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reactfunctpolym.2020.104550"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612822666160204120547"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1793"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2020.113625"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/9783527644827.ch6"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2005.06.007"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019266108"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13346\u2010018\u20100496\u20106"},{"key":"e_1_2_10_27_1","first-page":"389","volume-title":"Chemical Polysialylation of Recombinant Human Proteins, in Glyco\u2010Engineering: Methods and Protocols","author":"Smirnov I. 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