Chemical Synthesis of the Highly Hydrophobic Antiviral Membrane‐Associated Protein IFITM3 and Modified Variants
Interferon‐induced transmembrane protein 3 (IFITM3) is an antiviral transmembrane protein that is thought to serve as the primary factor for inhibiting the replication of a large number of viruses, including West Nile virus, Dengue virus, Ebola virus, and Zika virus. Production of this 14.5 kDa, 133...
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| Veröffentlicht in: | Angewandte Chemie 2017-10, Vol.129 (41), p.12813-12817 |
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| description | Interferon‐induced transmembrane protein 3 (IFITM3) is an antiviral transmembrane protein that is thought to serve as the primary factor for inhibiting the replication of a large number of viruses, including West Nile virus, Dengue virus, Ebola virus, and Zika virus. Production of this 14.5 kDa, 133‐residue transmembrane protein, especially with essential posttranslational modifications, by recombinant expression is challenging. In this report, we document the chemical synthesis of IFTIM3 in multi‐milligram quantities (>15 mg) and the preparation of phosphorylated and fluorescent variants. The synthesis was accomplished by using KAHA ligations, which operate under acidic aqueous/organic mixtures that excel at solubilizing even the exceptionally hydrophobic C‐terminal region of IFITM3. The synthetic material is readily incorporated into model vesicles and forms the basis for using synthetic, homogenous IFITM3 and its derivatives for further studying its structure and biological mode of action.
Das hydrophobe antivirale Membranprotein IFITM3 wurde durch chemoselektive Ligation unter sauren Bedingungen aufgebaut; dabei werden Estergruppen eingeführt, welche die Löslichkeit der Peptidsegmente erhöhen. Durch α‐Ketosäure‐Hydroxylamin(KAHA)‐Ligation erhaltene Depsipeptide wurden am Ende der Proteinsynthese in Amide umgelagert. |
| doi_str_mv | 10.1002/ange.201707554 |
| format | Article |
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Das hydrophobe antivirale Membranprotein IFITM3 wurde durch chemoselektive Ligation unter sauren Bedingungen aufgebaut; dabei werden Estergruppen eingeführt, welche die Löslichkeit der Peptidsegmente erhöhen. Durch α‐Ketosäure‐Hydroxylamin(KAHA)‐Ligation erhaltene Depsipeptide wurden am Ende der Proteinsynthese in Amide umgelagert.</description><identifier>ISSN: 0044-8249</identifier><identifier>EISSN: 1521-3757</identifier><identifier>DOI: 10.1002/ange.201707554</identifier><identifier>PMID: 32313320</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Chemical synthesis ; Chemische Proteinsynthese ; Chemistry ; Dengue fever ; Fluorescence ; Hydrophobicity ; IFITM3 ; Interferon ; KAHA-Ligation ; Membrane proteins ; Membranproteine ; Mode of action ; Proteinmodifikationen ; Proteins ; Vector-borne diseases ; Viral diseases ; Viruses ; West Nile virus ; Zuschrift ; Zuschriften</subject><ispartof>Angewandte Chemie, 2017-10, Vol.129 (41), p.12813-12817</ispartof><rights>2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.</rights><rights>2017. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3794-20ffb3a7eb5ef1f7b973b661babff2c5c79e7daf200b18a05e2416eed27f3e113</citedby><cites>FETCH-LOGICAL-c3794-20ffb3a7eb5ef1f7b973b661babff2c5c79e7daf200b18a05e2416eed27f3e113</cites><orcidid>0000-0001-8394-8910</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fange.201707554$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fange.201707554$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32313320$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Harmand, Thibault J.</creatorcontrib><creatorcontrib>Pattabiraman, Vijaya R.</creatorcontrib><creatorcontrib>Bode, Jeffrey W.</creatorcontrib><title>Chemical Synthesis of the Highly Hydrophobic Antiviral Membrane‐Associated Protein IFITM3 and Modified Variants</title><title>Angewandte Chemie</title><addtitle>Angew Chem Weinheim Bergstr Ger</addtitle><description>Interferon‐induced transmembrane protein 3 (IFITM3) is an antiviral transmembrane protein that is thought to serve as the primary factor for inhibiting the replication of a large number of viruses, including West Nile virus, Dengue virus, Ebola virus, and Zika virus. Production of this 14.5 kDa, 133‐residue transmembrane protein, especially with essential posttranslational modifications, by recombinant expression is challenging. In this report, we document the chemical synthesis of IFTIM3 in multi‐milligram quantities (>15 mg) and the preparation of phosphorylated and fluorescent variants. The synthesis was accomplished by using KAHA ligations, which operate under acidic aqueous/organic mixtures that excel at solubilizing even the exceptionally hydrophobic C‐terminal region of IFITM3. The synthetic material is readily incorporated into model vesicles and forms the basis for using synthetic, homogenous IFITM3 and its derivatives for further studying its structure and biological mode of action.
Das hydrophobe antivirale Membranprotein IFITM3 wurde durch chemoselektive Ligation unter sauren Bedingungen aufgebaut; dabei werden Estergruppen eingeführt, welche die Löslichkeit der Peptidsegmente erhöhen. Durch α‐Ketosäure‐Hydroxylamin(KAHA)‐Ligation erhaltene Depsipeptide wurden am Ende der Proteinsynthese in Amide umgelagert.</description><subject>Chemical synthesis</subject><subject>Chemische Proteinsynthese</subject><subject>Chemistry</subject><subject>Dengue fever</subject><subject>Fluorescence</subject><subject>Hydrophobicity</subject><subject>IFITM3</subject><subject>Interferon</subject><subject>KAHA-Ligation</subject><subject>Membrane proteins</subject><subject>Membranproteine</subject><subject>Mode of action</subject><subject>Proteinmodifikationen</subject><subject>Proteins</subject><subject>Vector-borne diseases</subject><subject>Viral diseases</subject><subject>Viruses</subject><subject>West Nile virus</subject><subject>Zuschrift</subject><subject>Zuschriften</subject><issn>0044-8249</issn><issn>1521-3757</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNqFkctuEzEUhi0EoqGwZYkssWEzwZeZcbxBiqK2idQAEoWtZc8cZ1xN7NSeFM2OR-AZeRIcpYTLhpUtne98Or9-hF5SMqWEsLfab2DKCBVEVFX5CE1oxWjBRSUeowkhZVnMWCnP0LOUbgkhNRPyKTrjjFPOGZmgu0UHW9foHn8a_dBBcgkHi_MPL92m60e8HNsYdl0wrsFzP7h7FzO9hq2J2sOPb9_nKYXG6QFa_DGGAZzHq8vVzZpj7Vu8Dq2zLs--6Oi0H9Jz9MTqPsGLh_ccfb68uFksi-sPV6vF_LpouJBlwYi1hmsBpgJLrTBScFPX1GhjLWuqRkgQrbaMEENnmlTASloDtExYDpTyc_Tu6N3tzRbaBvyQD1e76LY6jipop_6eeNepTbhXglayljIL3jwIYrjbQxrU1qUG-j7HDvukGJeccDGbiYy-_ge9DfvoczxFZXmgSEkyNT1STQwpRbCnYyhRhzbVoU11ajMvvPozwgn_VV8G5BH46noY_6NT8_dXF7_lPwHOWa7e</recordid><startdate>20171002</startdate><enddate>20171002</enddate><creator>Harmand, Thibault J.</creator><creator>Pattabiraman, Vijaya R.</creator><creator>Bode, Jeffrey W.</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8394-8910</orcidid></search><sort><creationdate>20171002</creationdate><title>Chemical Synthesis of the Highly Hydrophobic Antiviral Membrane‐Associated Protein IFITM3 and Modified Variants</title><author>Harmand, Thibault J. ; Pattabiraman, Vijaya R. ; Bode, Jeffrey W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3794-20ffb3a7eb5ef1f7b973b661babff2c5c79e7daf200b18a05e2416eed27f3e113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Chemical synthesis</topic><topic>Chemische Proteinsynthese</topic><topic>Chemistry</topic><topic>Dengue fever</topic><topic>Fluorescence</topic><topic>Hydrophobicity</topic><topic>IFITM3</topic><topic>Interferon</topic><topic>KAHA-Ligation</topic><topic>Membrane proteins</topic><topic>Membranproteine</topic><topic>Mode of action</topic><topic>Proteinmodifikationen</topic><topic>Proteins</topic><topic>Vector-borne diseases</topic><topic>Viral diseases</topic><topic>Viruses</topic><topic>West Nile virus</topic><topic>Zuschrift</topic><topic>Zuschriften</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Harmand, Thibault J.</creatorcontrib><creatorcontrib>Pattabiraman, Vijaya R.</creatorcontrib><creatorcontrib>Bode, Jeffrey W.</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Angewandte Chemie</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Harmand, Thibault J.</au><au>Pattabiraman, Vijaya R.</au><au>Bode, Jeffrey W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemical Synthesis of the Highly Hydrophobic Antiviral Membrane‐Associated Protein IFITM3 and Modified Variants</atitle><jtitle>Angewandte Chemie</jtitle><addtitle>Angew Chem Weinheim Bergstr Ger</addtitle><date>2017-10-02</date><risdate>2017</risdate><volume>129</volume><issue>41</issue><spage>12813</spage><epage>12817</epage><pages>12813-12817</pages><issn>0044-8249</issn><eissn>1521-3757</eissn><abstract>Interferon‐induced transmembrane protein 3 (IFITM3) is an antiviral transmembrane protein that is thought to serve as the primary factor for inhibiting the replication of a large number of viruses, including West Nile virus, Dengue virus, Ebola virus, and Zika virus. Production of this 14.5 kDa, 133‐residue transmembrane protein, especially with essential posttranslational modifications, by recombinant expression is challenging. In this report, we document the chemical synthesis of IFTIM3 in multi‐milligram quantities (>15 mg) and the preparation of phosphorylated and fluorescent variants. The synthesis was accomplished by using KAHA ligations, which operate under acidic aqueous/organic mixtures that excel at solubilizing even the exceptionally hydrophobic C‐terminal region of IFITM3. The synthetic material is readily incorporated into model vesicles and forms the basis for using synthetic, homogenous IFITM3 and its derivatives for further studying its structure and biological mode of action.
Das hydrophobe antivirale Membranprotein IFITM3 wurde durch chemoselektive Ligation unter sauren Bedingungen aufgebaut; dabei werden Estergruppen eingeführt, welche die Löslichkeit der Peptidsegmente erhöhen. Durch α‐Ketosäure‐Hydroxylamin(KAHA)‐Ligation erhaltene Depsipeptide wurden am Ende der Proteinsynthese in Amide umgelagert.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>32313320</pmid><doi>10.1002/ange.201707554</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0001-8394-8910</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Chemical synthesis Chemische Proteinsynthese Chemistry Dengue fever Fluorescence Hydrophobicity IFITM3 Interferon KAHA-Ligation Membrane proteins Membranproteine Mode of action Proteinmodifikationen Proteins Vector-borne diseases Viral diseases Viruses West Nile virus Zuschrift Zuschriften |
| title | Chemical Synthesis of the Highly Hydrophobic Antiviral Membrane‐Associated Protein IFITM3 and Modified Variants |
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