{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:58:54Z","timestamp":1788793134355,"version":"build-2803163510"},"reference-count":77,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["772280"],"award-info":[{"award-number":["772280"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RE2796\/6-1"],"award-info":[{"award-number":["RE2796\/6-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2021,6,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Eukaryotic mRNAs are emerging modalities for protein replacement therapy and vaccination. Their 5\u2032 cap is important for mRNA translation and immune response and can be naturally methylated at different positions by <jats:italic>S<\/jats:italic>\u2010adenosyl\u2010<jats:sc>l<\/jats:sc>\u2010methionine (AdoMet)\u2010dependent methyltransferases (MTases). We report on the cosubstrate scope of the MTase CAPAM responsible for methylation at the <jats:italic>N<\/jats:italic><jats:sup>6<\/jats:sup>\u2010position of adenosine start nucleotides using synthetic AdoMet analogs. The chemo\u2010enzymatic propargylation enabled production of site\u2010specifically modified reporter\u2010mRNAs. These cap\u2010propargylated mRNAs were efficiently translated and showed \u22483\u2010fold increased immune response in human cells. The same effects were observed when the receptor binding domain (RBD) of SARS\u2010CoV\u20102\u2014a currently tested epitope for mRNA vaccination\u2014was used. Site\u2010specific chemo\u2010enzymatic modification of eukaryotic mRNA may thus be a suitable strategy to modulate translation and immune response of mRNAs for future therapeutic applications.<\/jats:p>","DOI":"10.1002\/anie.202100352","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T20:27:51Z","timestamp":1616444871000},"page":"13280-13286","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Chemo\u2010Enzymatic Modification of the 5\u2032 Cap Maintains Translation and Increases Immunogenic Properties of mRNA"],"prefix":"10.1002","volume":"60","author":[{"given":"Melissa","family":"van D\u00fclmen","sequence":"first","affiliation":[{"name":"Department of Chemistry and Pharmacy Institute of Biochemistry  Corrensstrasse 36 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Muthmann","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Pharmacy Institute of Biochemistry  Corrensstrasse 36 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3107-4147","authenticated-orcid":false,"given":"Andrea","family":"Rentmeister","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Pharmacy Institute of Biochemistry  Corrensstrasse 36 48149 M\u00fcnster Germany"},{"name":"Cells in Motion Interfaculty Center University of M\u00fcnster  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,6]]},"reference":[{"key":"e_1_2_6_1_1","unstructured":"\u00a0"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2027906"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022483"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2798-3"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.0c00181"},{"key":"e_1_2_6_6_1","unstructured":"\u00a0"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.8.4710"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200001)30:1<1::AID-IMMU1>3.0.CO;2-#"},{"key":"e_1_2_6_9_1","unstructured":"\u00a0"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-07-033258"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10072"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.243"},{"key":"e_1_2_6_13_1","unstructured":"\u00a0"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4278"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2019.10.002"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.06.008"},{"key":"e_1_2_6_17_1","unstructured":"\u00a0"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3434"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.042"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132505"},{"key":"e_1_2_6_21_1","unstructured":"\u00a0"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1612444114"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515152113"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3527(00)55003-9"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa032"},{"key":"e_1_2_6_26_2","unstructured":"TrilinkBiotechnologies \u201cClean Cap\u201d can be found underhttps:\/\/www.trilinkbiotech.com\/cleancap 2020;"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00202-20"},{"key":"e_1_2_6_28_1","unstructured":"\u00a0"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.190306"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz751"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0231-8"},{"key":"e_1_2_6_32_1","unstructured":"\u00a0"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav0080"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-018-0117-4"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.06.006"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.05.030"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108038"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2016.02.001"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b02597"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201604107"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201604107"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202007111"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202007111"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.077099.120"},{"key":"e_1_2_6_43_1","unstructured":"\u00a0"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz084"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1039\/C9SC05981D"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2016.03.019"},{"key":"e_1_2_6_47_1","unstructured":"\u00a0"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201100781"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks381"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol501169y"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7CC08300A"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202013936"},{"key":"e_1_2_6_52_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202013936"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja2118333"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb2000567"},{"key":"e_1_2_6_55_1","unstructured":"\u00a0"},{"key":"e_1_2_6_56_2","unstructured":"CureVacAG \u201cA Study to Evaluate the Safety and Immunogenicity of Vaccine CVnCoV in Healthy Adults in Germany\u201d can be found underhttps:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT04674189 2021;"},{"key":"e_1_2_6_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2639-4"},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-020-00199-1"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(00)00002-8"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja808387g"},{"key":"e_1_2_6_61_1","unstructured":"\u00a0"},{"key":"e_1_2_6_62_2","first-page":"1486","volume":"7","author":"Stepinski J.","year":"2001","journal-title":"RNA"},{"key":"e_1_2_6_63_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol0167715"},{"key":"e_1_2_6_64_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.5430403"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506438200"},{"key":"e_1_2_6_66_1","unstructured":"\u00a0"},{"key":"e_1_2_6_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.06.014"},{"key":"e_1_2_6_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2018.09.011"},{"key":"e_1_2_6_69_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz6893"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2814-7"},{"key":"e_1_2_6_71_1","unstructured":"\u00a0"},{"key":"e_1_2_6_72_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035389"},{"key":"e_1_2_6_73_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034577"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00833-16"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202100352","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.202100352","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202100352","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T22:31:59Z","timestamp":1692657119000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202100352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,6]]},"references-count":77,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2021,6,7]]}},"alternative-id":["10.1002\/anie.202100352"],"URL":"https:\/\/doi.org\/10.1002\/anie.202100352","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,6]]},"assertion":[{"value":"2021-01-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}