Nucleic acid triggered catalytic drug and probe release: a new concept for the design of chemotherapeutic and diagnostic agents.
Recently, we described a new concept for the design of highly selective antiviral and anticancer chemotherapeutic agents that makes use of a disease-specific nucleic acid sequence to template the association of a prodrug with a catalyst which catalyzes the release of the drug. Herein, we report on the effect of mismatches, sterics, and electronics on the rate and specificity of drug and probe release in both two and three component model systems, and on the stability of the prodrug linker in human serum.
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Department of Chemistry, Campus Box 1134, Washington University, One Brookings Drive, St. Louis, MO 63130, USA.
Taylor
J S
JS
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D004273:DNA, Neoplasm / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D007700:Kinetics; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D013698:Templates, Genetic; D014468:Umbelliferones / Q000737:chemistry
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded; D004279:DNA, Viral; D011355:Prodrugs; D014468:Umbelliferones