Journal Article

PUBDB-2025-04336

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Drug targeting of protein-nucleic acid interactions

Genz, L.Extern*CSSB* ; Nair, S.CSSB* ; Sweeney, A.CSSB* ; Topf, M. (Corresponding author)Extern*CSSB*

2025
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.sbi.2025.103165  doi:10.3204/PUBDB-2025-04336

Abstract: Protein–nucleic acid interactions are vital to gene regulation and disease, yet have long been considered “undruggable.” Recent advances are reshaping this paradigm, enabling therapeutic targeting of DNA- and RNA-binding proteins. In this review, we highlight four major strategies: (1) direct disruption of protein-nucleic acid binding, (2) stabilization of specific complexes or conformations, (3) targeted degradation of interaction partners, and (4) allosteric modulation. We explore key examples across transcription factors, RNA-binding proteins, and DNA repair proteins, and emphasize emerging chemical, structural, and computational techniques that are accelerating discovery. Together, by intervening directly in the gene regulatory machinery, these approaches expand the druggable genome and open new avenues for treating cancer, genetic disorders, and viral infections.

Note: and DFG CRC1648

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Contributing Institute(s):

1. CSSB - Leibniz-Institut für Experimentelle Virologie (LIV) / UKE - Maya Topf (CSSB-LIV/UKE-MT)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Experiment(s):

1. No specific instrument

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; BIOSIS Reviews Reports And Meetings ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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