Research

A variety of recent research suggests that excess and dysregulation of conserved epitranscriptional RNA modifications are involved in the of phenotypes of various pathologies. Therefore, selective manipulation of the epitranscriptome with small-molecule drugs might provide an emerging treatment option for such diseases. We focus particularly on the development of selective covalent and non-covalent inhibitors of RNA methyltransferases by utilizing the contemporary MedChem technologies. See also Transregio 319 RMaP.

Key publications:

Nanomole Scale Screening of Fluorescent RNA-Methyltransferase Probes Enables the Discovery of METTL1 Inhibitors

Meidner JL, Frey AF, Zimmermann RA, Sabin MO, Nidoieva Z, Weldert AC, Hoba SN, Krone MW, Barthels F.* Angew Chem 2024, 63(48), e202403792.

 

A microscale thermophoresis-based enzymatic RNA methyltransferase assay enables the discovery of DNMT2 inhibitors

Nidoieva Z, Sabin MO, Dewald T, Weldert AC, Hoba SN, Helm M, Barthels F.* Commun Chem 2025, 8(1), 1–9.

 

Structure-guided design of a methyltransferase-like 3 (METTL3) proteolysis targeting chimera (PROTAC) incorporating an indole–nicotinamide chemotype

Weldert AC, Frey AF, Krone MW, Krähe F, Kuhn H, Kersten C, Barthels F.* RSC MedChem 2025, D5MD00359H.

 

DNA-encoded Library Screening Uncovers Potent DNMT2 Inhibitors Targeting a Cryptic Allosteric Binding Site

Frey AF, Schwan M, Weldert AC, Kadenbach V, Kopp J, Nidoieva Z, Zimmermann RA, Gleue L, Zimmer C, Jörg M, Friedland K, Helm M, Sinning I, Barthels F.* iScience 2025, accepted.

 

Non-covalent dyes in microscale thermophoresis for studying RNA ligand interactions and modifications

Kallert E, Behrendt M, Frey AF, Kersten, C, Barthels F.* Chem Sci 2023, 14(36), 9827–9837.