{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:07:51Z","timestamp":1788314871550,"version":"build-2803163510"},"reference-count":33,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T00:00:00Z","timestamp":1550707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund","doi-asserted-by":"publisher","award":["NPRP6-065-3-012"],"award-info":[{"award-number":["NPRP6-065-3-012"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","em-consulte.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomedicine &amp; Pharmacotherapy"],"published-print":{"date-parts":[[2019,4]]},"DOI":"10.1016\/j.biopha.2019.108725","type":"journal-article","created":{"date-parts":[[2019,2,28]],"date-time":"2019-02-28T05:17:28Z","timestamp":1551331048000},"page":"108725","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["Production of \u201cbiobetter\u201d variants of glucarpidase with enhanced enzyme activity"],"prefix":"10.1016","volume":"112","author":[{"given":"Alanod D.","family":"Al-Qahtani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara S.","family":"Bashraheel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma B.","family":"Rashidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. David","family":"O\u2019Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atilio Reyes","family":"Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Domling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayed K.","family":"Goda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.biopha.2019.108725_bib0005","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1517\/13543776.10.2.209","article-title":"The potential use of carboxypeptidase G2 in the treatment of cancer","volume":"10","author":"Burke","year":"2000","journal-title":"Expert Opin. Ther. Pat."},{"key":"10.1016\/j.biopha.2019.108725_bib0010","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.addr.2017.09.009","article-title":"Antibody directed enzyme prodrug therapy (ADEPT): trials and tribulations","volume":"118","author":"Sharma","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"issue":"1","key":"10.1016\/j.biopha.2019.108725_bib0015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/14712598.2017.1247802","article-title":"Translating antibody directed enzyme prodrug therapy (ADEPT) and prospects for combination","volume":"17","author":"Sharma","year":"2017","journal-title":"Expert Opin. Biol. Ther."},{"key":"10.1016\/j.biopha.2019.108725_bib0020","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2174\/1874104501812010111","article-title":"Therapeutic potential of prodrugs towards targeted drug delivery","volume":"12","author":"Mishra","year":"2018","journal-title":"Open Med. Chem. J."},{"issue":"3-4","key":"10.1016\/j.biopha.2019.108725_bib0025","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3109\/10428190009089446","article-title":"Carboxypeptidase G2 rescue in delayed methotrexate elimination in renal failure","volume":"37","author":"Mohty","year":"2000","journal-title":"Leuk. Lymphoma"},{"key":"10.1016\/j.biopha.2019.108725_bib0030","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/sj.bjc.6602337","article-title":"Carboxypeptidase G2 rescue in patients with methotrexate intoxication and renal failure","volume":"92","author":"Buchen","year":"2005","journal-title":"Br. J. Cancer"},{"issue":"Jan (1)","key":"10.1016\/j.biopha.2019.108725_bib0035","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1634\/theoncologist.2017-0243","article-title":"Consensus guideline for use of glucarpidase in patients with high-dose methotrexate induced acute kidney injury and delayed methotrexate clearance","volume":"23","author":"Ramsey","year":"2018","journal-title":"Oncologist"},{"issue":"May (4)","key":"10.1016\/j.biopha.2019.108725_bib0040","first-page":"204","article-title":"Do not exclude glucarpidase too soon in the context of high-dose methotrexate induced nephrotoxicity","volume":"76","author":"dLD","year":"2018","journal-title":"Neth. J. Med."},{"issue":"April (Suppl 1)","key":"10.1016\/j.biopha.2019.108725_bib0045","doi-asserted-by":"crossref","first-page":"S103","DOI":"10.1016\/j.nephro.2018.02.015","article-title":"Renal toxicity of high-dose methotrexate","volume":"14","author":"Garcia","year":"2018","journal-title":"Nephrol. Ther."},{"key":"10.1016\/j.biopha.2019.108725_bib0050","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrg3927","article-title":"Methods for the directed evolution of proteins","volume":"16","author":"Packer","year":"2015","journal-title":"Nat. Rev. Genet."},{"issue":"8","key":"10.1016\/j.biopha.2019.108725_bib0055","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/11737","article-title":"Evolution of a cytokine using DNA family shuffling","volume":"17","author":"Chang","year":"1999","journal-title":"Nat. Biotechnol."},{"issue":"9","key":"10.1016\/j.biopha.2019.108725_bib0060","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/12884","article-title":"DNA shuffling of subgenomic sequences of subtilisin","volume":"17","author":"Ness","year":"1999","journal-title":"Nat. Biotechnol."},{"issue":"3","key":"10.1016\/j.biopha.2019.108725_bib0065","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/7003","article-title":"Directed evolution of thymidine kinase for AZT phosphorylation using DNA family shuffling","volume":"17","author":"Christians","year":"1999","journal-title":"Nat. Biotechnol."},{"issue":"5","key":"10.1016\/j.biopha.2019.108725_bib0070","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1002\/(SICI)1097-0290(19990605)63:5<544::AID-BIT4>3.0.CO;2-6","article-title":"Tuning biphenyl dioxygenase for extended substrate specificity","volume":"63","author":"Bruhlmann","year":"1999","journal-title":"Biotechnol. Bioeng."},{"issue":"6","key":"10.1016\/j.biopha.2019.108725_bib0075","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1093\/nar\/25.6.1307","article-title":"Optimization of DNA shuffling for high fidelity recombination","volume":"25","author":"Zhao","year":"1997","journal-title":"Nucleic Acids Res."},{"issue":"1","key":"10.1016\/j.biopha.2019.108725_bib0080","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0378-1119(99)00240-1","article-title":"Novel family shuffling methods for the in vitro evolution of enzymes","volume":"236","author":"Kikuchi","year":"1999","journal-title":"Gene"},{"issue":"5","key":"10.1016\/j.biopha.2019.108725_bib0085","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s00449-018-1906-3","article-title":"Genome shuffling and ribosome engineering of Streptomyces virginiae for improved virginiamycin production","volume":"41","author":"Tong","year":"2018","journal-title":"Bioprocess Biosyst. Eng."},{"issue":"22","key":"10.1016\/j.biopha.2019.108725_bib0090","doi-asserted-by":"crossref","first-page":"10747","DOI":"10.1073\/pnas.91.22.10747","article-title":"DNA shuffling by random fragmentation and reassembly: in vitro recombination for molecular evolution","volume":"91","author":"Stemmer","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"9-10","key":"10.1016\/j.biopha.2019.108725_bib0095","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s10930-009-9211-2","article-title":"Functional overexpression and purification of a codon optimized synthetic glucarpidase (carboxypeptidase G2) in Escherichia coli","volume":"28","author":"Goda","year":"2009","journal-title":"Protein J."},{"issue":"4","key":"10.1016\/j.biopha.2019.108725_bib0100","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0196254","article-title":"Isolation and molecular characterization of novel glucarpidases: enzymes to improve the antibody directed enzyme pro-drug therapy for cancer treatment","volume":"13","author":"Rashidi","year":"2018","journal-title":"PLoS One"},{"issue":"23","key":"10.1016\/j.biopha.2019.108725_bib0105","doi-asserted-by":"crossref","first-page":"7207","DOI":"10.1016\/S0021-9258(19)45873-0","article-title":"Purification and properties of carboxypeptidase G 1","volume":"246","author":"McCullough","year":"1971","journal-title":"J. Biol. Chem."},{"issue":"3","key":"10.1016\/j.biopha.2019.108725_bib0110","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/bioinformatics\/btt691","article-title":"mCSM: predicting the effects of mutations in proteins using graph-based signatures","volume":"30","author":"Pires DE AD","year":"2014","journal-title":"Bioinformatics"},{"issue":"W1","key":"10.1016\/j.biopha.2019.108725_bib0115","doi-asserted-by":"crossref","first-page":"W229","DOI":"10.1093\/nar\/gkx439","article-title":"SDM: a server for predicting effects of mutations on protein stability","volume":"45","author":"Pandurangan","year":"2017","journal-title":"Nucleic Acids Res."},{"issue":"web Server issue","key":"10.1016\/j.biopha.2019.108725_bib0120","doi-asserted-by":"crossref","first-page":"W314","DOI":"10.1093\/nar\/gku411","article-title":"DUET: a server for predicting effects of mutations on protein stability using an integrated computational approach","volume":"42","author":"Pires","year":"2014","journal-title":"Nucleic Acids Res."},{"issue":"3","key":"10.1016\/j.biopha.2019.108725_bib0125","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative protein modelling by satisfaction of spatial restraints","volume":"234","author":"Sali","year":"1993","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.biopha.2019.108725_bib0130","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev.biophys.29.1.291","article-title":"Comparative protein structure modeling of genes and genomes","volume":"29","author":"Marti-Renom","year":"2000","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"issue":"9","key":"10.1016\/j.biopha.2019.108725_bib0135","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1110\/ps.9.9.1753","article-title":"Modeling of loops in protein structures","volume":"9","author":"Fiser","year":"2000","journal-title":"Protein Sci."},{"key":"10.1016\/j.biopha.2019.108725_bib0140","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-1-4939-7231-9_4","article-title":"Protein structure modeling with MODELLER","volume":"1654","author":"Webb","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.biopha.2019.108725_bib0145","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ejps.2018.10.014","article-title":"Production of \"biobetter\" glucarpidase variants to improve drug detoxification and antibody directed enzyme prodrug therapy for cancer treatment","volume":"127","author":"AlQahtani","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"issue":"3","key":"10.1016\/j.biopha.2019.108725_bib0150","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1128\/jb.156.3.1222-1227.1983","article-title":"Molecular cloning of the Pseudomonas carboxypeptidase G2 gene and its expression in Escherichia coli and Pseudomonas putida","volume":"156","author":"Minton","year":"1983","journal-title":"J. Bacteriol."},{"issue":"2","key":"10.1016\/j.biopha.2019.108725_bib0155","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1000002","article-title":"How protein stability and new functions trade off","volume":"4","author":"Tokuriki","year":"2008","journal-title":"PLoS Comput. Biol."},{"issue":"8","key":"10.1016\/j.biopha.2019.108725_bib0160","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.bbapap.2010.11.005","article-title":"Protein stability, flexibility and function","volume":"1814","author":"Teilum","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"issue":"1","key":"10.1016\/j.biopha.2019.108725_bib0165","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/S0006-3495(98)77529-0","article-title":"A helix propensity scale based on experimental studies of peptides and proteins","volume":"75","author":"Pace","year":"1998","journal-title":"Biophys. J."}],"container-title":["Biomedicine &amp; Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332219301416?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332219301416?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T17:36:41Z","timestamp":1778693801000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0753332219301416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4]]},"references-count":33,"alternative-id":["S0753332219301416"],"URL":"https:\/\/doi.org\/10.1016\/j.biopha.2019.108725","relation":{},"ISSN":["0753-3322"],"issn-type":[{"value":"0753-3322","type":"print"}],"subject":[],"published":{"date-parts":[[2019,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Production of \u201cbiobetter\u201d variants of glucarpidase with enhanced enzyme activity","name":"articletitle","label":"Article Title"},{"value":"Biomedicine & Pharmacotherapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biopha.2019.108725","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Authors. Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"108725"}}