Chemical biology and medicinal chemistry of RNA methyltransferases

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Tim R Fischer
  • Laurenz Meidner
  • Marvin Schwickert
  • Marlies Weber
  • Robert A Zimmermann
  • Christian Kersten
  • Tanja Schirmeister
  • Mark Helm
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000786341600001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1093/nar/gkac224
eISSN
1362-4962
Externe Identifier
  • Clarivate Analytics Document Solution ID: 1A2JR
  • PubMed Identifier: 35412633
ISSN
0305-1048
Ausgabe der Veröffentlichung
8
Zeitschrift
NUCLEIC ACIDS RESEARCH
Paginierung
4216 - 4245
Datum der Veröffentlichung
2022
Status
Published
Titel
Chemical biology and medicinal chemistry of RNA methyltransferases
Sub types
  • Article
Ausgabe der Zeitschrift
50

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Abstract
<jats:title>Abstract</jats:title><jats:p>RNA methyltransferases (MTases) are ubiquitous enzymes whose hitherto low profile in medicinal chemistry, contrasts with the surging interest in RNA methylation, the arguably most important aspect of the new field of epitranscriptomics. As MTases become validated as drug targets in all major fields of biomedicine, the development of small molecule compounds as tools and inhibitors is picking up considerable momentum, in academia as well as in biotech. Here we discuss the development of small molecules for two related aspects of chemical biology. Firstly, derivates of the ubiquitous cofactor S-adenosyl-l-methionine (SAM) are being developed as bioconjugation tools for targeted transfer of functional groups and labels to increasingly visible targets. Secondly, SAM-derived compounds are being investigated for their ability to act as inhibitors of RNA MTases. Drug development is moving from derivatives of cosubstrates towards higher generation compounds that may address allosteric sites in addition to the catalytic centre. Progress in assay development and screening techniques from medicinal chemistry have led to recent breakthroughs, e.g. in addressing human enzymes targeted for their role in cancer. Spurred by the current pandemic, new inhibitors against coronaviral MTases have emerged at a spectacular rate, including a repurposed drug which is now in clinical trial.</jats:p>
Autoren
  • Tim R Fischer
  • Laurenz Meidner
  • Marvin Schwickert
  • Marlies Weber
  • Robert A Zimmermann
  • Christian Kersten
  • Tanja Schirmeister
  • Mark Helm
DOI
10.1093/nar/gkac224
eISSN
1362-4962
ISSN
0305-1048
Ausgabe der Veröffentlichung
8
Zeitschrift
Nucleic Acids Research
Sprache
en
Online publication date
2022
Paginierung
4216 - 4245
Datum der Veröffentlichung
2022
Status
Published
Herausgeber
Oxford University Press (OUP)
Herausgeber URL
http://dx.doi.org/10.1093/nar/gkac224
Datum der Datenerfassung
2023
Titel
Chemical biology and medicinal chemistry of RNA methyltransferases
Ausgabe der Zeitschrift
50

Datenquelle: Crossref

Abstract
RNA methyltransferases (MTases) are ubiquitous enzymes whose hitherto low profile in medicinal chemistry, contrasts with the surging interest in RNA methylation, the arguably most important aspect of the new field of epitranscriptomics. As MTases become validated as drug targets in all major fields of biomedicine, the development of small molecule compounds as tools and inhibitors is picking up considerable momentum, in academia as well as in biotech. Here we discuss the development of small molecules for two related aspects of chemical biology. Firstly, derivates of the ubiquitous cofactor S-adenosyl-l-methionine (SAM) are being developed as bioconjugation tools for targeted transfer of functional groups and labels to increasingly visible targets. Secondly, SAM-derived compounds are being investigated for their ability to act as inhibitors of RNA MTases. Drug development is moving from derivatives of cosubstrates towards higher generation compounds that may address allosteric sites in addition to the catalytic centre. Progress in assay development and screening techniques from medicinal chemistry have led to recent breakthroughs, e.g. in addressing human enzymes targeted for their role in cancer. Spurred by the current pandemic, new inhibitors against coronaviral MTases have emerged at a spectacular rate, including a repurposed drug which is now in clinical trial.
Addresses
  • Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg-University Mainz, Staudingerweg 5, 55128Mainz, Germany.
Autoren
  • Tim R Fischer
  • Laurenz Meidner
  • Marvin Schwickert
  • Marlies Weber
  • Robert A Zimmermann
  • Christian Kersten
  • Tanja Schirmeister
  • Mark Helm
DOI
10.1093/nar/gkac224
eISSN
1362-4962
Externe Identifier
  • PubMed Identifier: 35412633
  • PubMed Central ID: PMC9071492
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft: HE3397/17-1
  • Deutsche Forschungsgemeinschaft: TP C01
  • Deutsche Forschungsgemeinschaft: TRR319 RMaP TP A01
  • Deutsche Forschungsgemeinschaft: SPP1784
  • Deutsche Forschungsgemeinschaft: TRR319 RMaP
Open access
true
ISSN
0305-1048
Ausgabe der Veröffentlichung
8
Zeitschrift
Nucleic acids research
Schlüsselwörter
  • Humans
  • Methyltransferases
  • S-Adenosylmethionine
  • RNA
  • Drug Development
Sprache
eng
Medium
Print
Open access status
Open Access
Paginierung
4216 - 4245
Datum der Veröffentlichung
2022
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2022
Titel
Chemical biology and medicinal chemistry of RNA methyltransferases.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
50

Files

https://academic.oup.com/nar/article-pdf/50/8/4216/43546924/gkac224.pdf https://europepmc.org/articles/PMC9071492?pdf=render

Datenquelle: Europe PubMed Central

Abstract
RNA methyltransferases (MTases) are ubiquitous enzymes whose hitherto low profile in medicinal chemistry, contrasts with the surging interest in RNA methylation, the arguably most important aspect of the new field of epitranscriptomics. As MTases become validated as drug targets in all major fields of biomedicine, the development of small molecule compounds as tools and inhibitors is picking up considerable momentum, in academia as well as in biotech. Here we discuss the development of small molecules for two related aspects of chemical biology. Firstly, derivates of the ubiquitous cofactor S-adenosyl-l-methionine (SAM) are being developed as bioconjugation tools for targeted transfer of functional groups and labels to increasingly visible targets. Secondly, SAM-derived compounds are being investigated for their ability to act as inhibitors of RNA MTases. Drug development is moving from derivatives of cosubstrates towards higher generation compounds that may address allosteric sites in addition to the catalytic centre. Progress in assay development and screening techniques from medicinal chemistry have led to recent breakthroughs, e.g. in addressing human enzymes targeted for their role in cancer. Spurred by the current pandemic, new inhibitors against coronaviral MTases have emerged at a spectacular rate, including a repurposed drug which is now in clinical trial.
Date of acceptance
2022
Autoren
  • Tim R Fischer
  • Laurenz Meidner
  • Marvin Schwickert
  • Marlies Weber
  • Robert A Zimmermann
  • Christian Kersten
  • Tanja Schirmeister
  • Mark Helm
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/35412633
DOI
10.1093/nar/gkac224
eISSN
1362-4962
Externe Identifier
  • PubMed Central ID: PMC9071492
Ausgabe der Veröffentlichung
8
Zeitschrift
Nucleic Acids Res
Schlüsselwörter
  • Drug Development
  • Humans
  • Methyltransferases
  • RNA
  • S-Adenosylmethionine
Sprache
eng
Country
England
Paginierung
4216 - 4245
PII
6567480
Datum der Veröffentlichung
2022
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Titel
Chemical biology and medicinal chemistry of RNA methyltransferases.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
50

Datenquelle: PubMed

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