Value Proposition
· Demonstrated selectivity (40x) for production of DNA-protein cross link (DPC) formation as compared to DNA-DNA interstrand cross-link (ICL) formation.
· Robust DPC formation shown in both nucleosome core particles and live human cell lines.
· High yield of DNA-protein cross links with similar cellular toxicity as traditional methods.
· Elucidated mechanism of action explaining permanence of DPCs formed by this agent.
Unmet Need
· DNA-protein cross-links (DPCs) and DNA-DNA interstrand cross-links (ICLs) both impact DNA unwinding, replication and transcription. Additionally, endogenous pathways to repair DPCs present opportunities to study and leverage therapeutic DNA repair (Housh, 2021). However, existing laboratory methods preferentially generate interstrand crosslinks (ICLs), limiting the ability to study DNA-protein crosslinks (DPCs) and their cellular effects. Thus, there exists a strong need for the development of an agent that reliably produces DPCs for the purpose of laboratory experimentation.
Technology Description
· Current methods for treating and studying DPCs are limited by cytotoxicity and low yields. Researchers at Johns Hopkins have developed a chemical agent that is highly specific for the production of DPCs.
Stage of Development
· In vitro experiments have been completed, demonstrating strong selectivity for DPCs compared to standard methods.
· Studies confirming cytotoxicity in live cell lines have been concluded, and preliminary assessment of the agent’s mechanism of action have also been conducted. [SB1]
Data Availability
· Data available upon request.
Publication
· Jiang X, Vu S, Yu H, Greenberg MM. Examination of a Chimeric Bis-Electrophile for Selective DNA-Protein Cross-Linking and Mechlorethamine Reveals an Unknown Source of Nitrogen Mustard Cytotoxicity. J Am Chem Soc. 2025 Sep 3;147(35):31839-31848. doi: 10.1021/jacs.5c09293. Epub 2025 Aug 19. PMID: 40828618; PMCID: PMC12451994.
