Peptides Targeting RNA m 6 A Methylations Influence the Viability of Cancer Cells
N6-methyladenosine (m A) is the most abundant nucleotide modification observed in eukaryotic mRNA. Changes in m A levels in transcriptome are tightly correlated to expression levels of m A methyltransferases and demethylases. Abnormal expression levels of methyltransferases and demethylases are obse...
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| Veröffentlicht in: | ChemMedChem 2023-02, Vol.18 (4), p.e202200549 |
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| creator | Rauff, Rushdhi Abedeera, Sudeshi M Schmocker, Stefani Xie, Jiale Abeysirigunawardena, Sanjaya C |
| description | N6-methyladenosine (m
A) is the most abundant nucleotide modification observed in eukaryotic mRNA. Changes in m
A levels in transcriptome are tightly correlated to expression levels of m
A methyltransferases and demethylases. Abnormal expression levels of methyltransferases and demethylases are observed in various diseases and health conditions such as cancer, male infertility, and obesity. This research explores the efficacy of m
A-modified RNA as an anticancer drug target. We discovered a 12-mer peptide that binds specifically to m
A-modified RNA using phage display experiments. Our fluorescence-based assays illustrate the selected peptide binds to methylated RNA with lower micromolar affinity and inhibit the binding of protein FTO, a demethylase enzyme specific to m
A modification. When cancer cell lines were treated with mtp1, it led to an increase in m
A levels and a decrease in cell viability. Hence our results illustrate the potential of mtp1 to be developed as a drug for cancer. |
| doi_str_mv | 10.1002/cmdc.202200549 |
| format | Article |
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A) is the most abundant nucleotide modification observed in eukaryotic mRNA. Changes in m
A levels in transcriptome are tightly correlated to expression levels of m
A methyltransferases and demethylases. Abnormal expression levels of methyltransferases and demethylases are observed in various diseases and health conditions such as cancer, male infertility, and obesity. This research explores the efficacy of m
A-modified RNA as an anticancer drug target. We discovered a 12-mer peptide that binds specifically to m
A-modified RNA using phage display experiments. Our fluorescence-based assays illustrate the selected peptide binds to methylated RNA with lower micromolar affinity and inhibit the binding of protein FTO, a demethylase enzyme specific to m
A modification. When cancer cell lines were treated with mtp1, it led to an increase in m
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A levels in transcriptome are tightly correlated to expression levels of m
A methyltransferases and demethylases. Abnormal expression levels of methyltransferases and demethylases are observed in various diseases and health conditions such as cancer, male infertility, and obesity. This research explores the efficacy of m
A-modified RNA as an anticancer drug target. We discovered a 12-mer peptide that binds specifically to m
A-modified RNA using phage display experiments. Our fluorescence-based assays illustrate the selected peptide binds to methylated RNA with lower micromolar affinity and inhibit the binding of protein FTO, a demethylase enzyme specific to m
A modification. When cancer cell lines were treated with mtp1, it led to an increase in m
A levels and a decrease in cell viability. Hence our results illustrate the potential of mtp1 to be developed as a drug for cancer.</description><subject>Alpha-Ketoglutarate-Dependent Dioxygenase FTO - metabolism</subject><subject>Humans</subject><subject>Male</subject><subject>Methylation</subject><subject>Methyltransferases - metabolism</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - metabolism</subject><subject>RNA - metabolism</subject><subject>RNA, Messenger - genetics</subject><issn>1860-7179</issn><issn>1860-7187</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kEtPwzAQhC0EoqVw5Yj8B1LWiR07xyjiUak8VbhGtrNujfKo4vTQf0-qQi87q9HMavURcstgzgDie9tUdh5DHAMInp2RKVMpRJIpeX7aZTYhVyH8AHCumLokkyQVqeRSTcnHO24HX2GgK92vcfDtmn6-5rShKc3pCw6bfa0H37WBLlpX77C1SIcN0m-vja_9sKedo4Ue7Z4WWNfhmlw4XQe8-dMZ-Xp8WBXP0fLtaVHky8gyLrMoY2idQQEi05WxjLFxCGetTBUXYF2CDjOLgisYXzVaVuC0skIaNE6aZEbmx7u270Lo0ZXb3je635cMygOb8sCmPLEZC3fHwnZnGqxO8X8YyS_3O2Au</recordid><startdate>20230214</startdate><enddate>20230214</enddate><creator>Rauff, Rushdhi</creator><creator>Abedeera, Sudeshi M</creator><creator>Schmocker, Stefani</creator><creator>Xie, Jiale</creator><creator>Abeysirigunawardena, Sanjaya C</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0003-2428-1962</orcidid><orcidid>https://orcid.org/0000-0001-5524-4131</orcidid><orcidid>https://orcid.org/0000-0002-3263-3545</orcidid><orcidid>https://orcid.org/0000-0003-4053-8991</orcidid></search><sort><creationdate>20230214</creationdate><title>Peptides Targeting RNA m 6 A Methylations Influence the Viability of Cancer Cells</title><author>Rauff, Rushdhi ; Abedeera, Sudeshi M ; Schmocker, Stefani ; Xie, Jiale ; Abeysirigunawardena, Sanjaya C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1479-91ecfbe5059adbc111bc15fcc768450cf3efe9ce5480747ba7d0fa8c57bebf7b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Alpha-Ketoglutarate-Dependent Dioxygenase FTO - metabolism</topic><topic>Humans</topic><topic>Male</topic><topic>Methylation</topic><topic>Methyltransferases - metabolism</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - metabolism</topic><topic>RNA - metabolism</topic><topic>RNA, Messenger - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rauff, Rushdhi</creatorcontrib><creatorcontrib>Abedeera, Sudeshi M</creatorcontrib><creatorcontrib>Schmocker, Stefani</creatorcontrib><creatorcontrib>Xie, Jiale</creatorcontrib><creatorcontrib>Abeysirigunawardena, Sanjaya C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>ChemMedChem</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rauff, Rushdhi</au><au>Abedeera, Sudeshi M</au><au>Schmocker, Stefani</au><au>Xie, Jiale</au><au>Abeysirigunawardena, Sanjaya C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Peptides Targeting RNA m 6 A Methylations Influence the Viability of Cancer Cells</atitle><jtitle>ChemMedChem</jtitle><addtitle>ChemMedChem</addtitle><date>2023-02-14</date><risdate>2023</risdate><volume>18</volume><issue>4</issue><spage>e202200549</spage><pages>e202200549-</pages><issn>1860-7179</issn><eissn>1860-7187</eissn><abstract>N6-methyladenosine (m
A) is the most abundant nucleotide modification observed in eukaryotic mRNA. Changes in m
A levels in transcriptome are tightly correlated to expression levels of m
A methyltransferases and demethylases. Abnormal expression levels of methyltransferases and demethylases are observed in various diseases and health conditions such as cancer, male infertility, and obesity. This research explores the efficacy of m
A-modified RNA as an anticancer drug target. We discovered a 12-mer peptide that binds specifically to m
A-modified RNA using phage display experiments. Our fluorescence-based assays illustrate the selected peptide binds to methylated RNA with lower micromolar affinity and inhibit the binding of protein FTO, a demethylase enzyme specific to m
A modification. When cancer cell lines were treated with mtp1, it led to an increase in m
A levels and a decrease in cell viability. Hence our results illustrate the potential of mtp1 to be developed as a drug for cancer.</abstract><cop>Germany</cop><pmid>36567478</pmid><doi>10.1002/cmdc.202200549</doi><orcidid>https://orcid.org/0000-0003-2428-1962</orcidid><orcidid>https://orcid.org/0000-0001-5524-4131</orcidid><orcidid>https://orcid.org/0000-0002-3263-3545</orcidid><orcidid>https://orcid.org/0000-0003-4053-8991</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | ChemMedChem, 2023-02, Vol.18 (4), p.e202200549 |
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| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Alpha-Ketoglutarate-Dependent Dioxygenase FTO - metabolism Humans Male Methylation Methyltransferases - metabolism Neoplasms - drug therapy Neoplasms - metabolism RNA - metabolism RNA, Messenger - genetics |
| title | Peptides Targeting RNA m 6 A Methylations Influence the Viability of Cancer Cells |
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