ArticleACS chemical biology2014
Platinum-RNA modifications following drug treatment in S. cerevisiae identified by click chemistry and enzymatic mapping.
Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- Chemotherapeutic Potential of Fluorouracil-Platinum (IV) Prodrugs Against Cisplatin-Resistant Colorectal Cancer Cells.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Noble Metal Complexes and Non-Canonical Nucleic Acids: From G-Quadruplex Recognition to Emerging Functional Architectures.Biomolecules · 2026Review
- Transcriptome-wide mapping reveals an RNA-dependent mechanism of platinum cancer drugs.bioRxiv : the preprint server for biology · 2025Article
- Ru(II) Complex-Mediated Phase Separation Amplifies Photocatalytic RNA Damage to Stimulate RIG‑I Immunotherapy.JACS Au · 2025Article
- The unique Pt(II)-induced nucleolar stress response and its deviation from DNA damage response pathways.The Journal of biological chemistry · 2024Article
- Ribosome Assembly and Repair.Annual review of cell and developmental biology · 2024Review
- Click-Capable Phenanthriplatin Derivatives as Tools to Study Pt(II)-Induced Nucleolar Stress.ACS chemical biology · 2024Article
- A clickable melphalan for monitoring DNA interstrand crosslink accumulation and detecting ICL repair defects in Fanconi anemia patient cells.Nucleic acids research · 2023Article
- PD-1/PD-L1 and DNA Damage Response in Cancer.Cells · 2023Review
- Targeting RNA structures with small molecules.Nature reviews. Drug discovery · 2022Review
- Clickable Cisplatin Derivatives as Versatile Tools to Probe the DNA Damage Response to Chemotherapy.Frontiers in oncology · 2022Article
- Exploiting azide-alkyne click chemistry in the synthesis, tracking and targeting of platinum anticancer complexes.Current opinion in chemical biology · 2020Review
- Nucleolar Stress Induction by Oxaliplatin and Derivatives.Journal of the American Chemical Society · 2019Article
- A cross-linking approach to map small molecule-RNA binding sites in cells.Bioorganic & medicinal chemistry letters · 2019Article
- Evidence for ligandable sites in structured RNA throughout the Protein Data Bank.Bioorganic & medicinal chemistry · 2019Article
- Effect of in vivo post-translational modifications of the HMGB1 protein upon binding to platinated DNA: a molecular simulation study.Nucleic acids research · 2018Article
- Pt-induced crosslinks promote target enrichment and protection from serum nucleases.Journal of inorganic biochemistry · 2018Article
- Using Genome Sequence to Enable the Design of Medicines and Chemical Probes.Chemical reviews · 2018Review
- Mapping platinum adducts on yeast ribosomal RNA using high-throughput sequencing.Chemical communications (Cambridge, England) · 2017Article
- Cu(II)-Based Paramagnetic Probe to Study RNA-Protein Interactions by NMR.Inorganic chemistry · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
With the importance of RNA-based regulatory pathways, the potential for targeting noncoding and coding RNAs by small molecule therapeutics is of great interest. Platinum(II) complexes including cisplatin (cis-diamminedichloroplatinum(II)) are widely prescribed anticancer compounds that form stable adducts on nucleic acids. In tumors, DNA damage from Pt(II) initiates apoptotic signaling, but this activity is not necessary for cytotoxicity (e.g., Yu et al., 2008), suggesting accumulation and consequences of Pt(II) lesions on non-DNA targets. We previously reported an azide-functionalized compound, picazoplatin, designed for post-treatment click labeling that enables detection of Pt complexes (White et al., 2013). Here, we report in-gel fluorescent detection of Pt-bound rRNA and tRNA extracted from picazoplatin-treated S. cerevisiae and labeled using Cu-free click chemistry. These data provide the first evidence that cellular tRNA is a platinum drug substrate. We assess Pt(II) binding sites within rRNA from cisplatin-treated S. cerevisiae, in regions where damage is linked to significant downstream consequences including the sarcin-ricin loop (SRL) Helix 95. Pt-RNA adducts occur on the nucleotide substrates of ribosome-inactivating proteins, as well as on the bulged-G motif critical for elongation factor recognition of the loop. At therapeutically relevant concentrations, Pt(II) also binds robustly within conserved cation-binding pockets in Domains V and VI rRNA at the peptidyl transferase center. Taken together, these results demonstrate a convenient click chemistry methodology that can be applied to identify other metal or covalent modification-based drug targets and suggest a ribotoxic mechanism for cisplatin cytotoxicity.
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