Model Systems for Activation of Nucleic Acid Encoded Prodrugs

Abstract

The development of more selective chemotherapeutic agents for benign treatments of malicious diseases is highly desirable. In recent years model systems for the release of small molecule drugs from nucleic acid conjugates by templated chemical or photochemical reactions have been designed. Common for these systems is that the stoichiometric or catalytic drug release is controlled by the highly selective hybridization between complementary strands of nucleic acids. Herein, the concepts of the new field of nucleic acid templated release reactions are outlined.

Effective Molarity Redux: Proximity as a Guiding Force in Chemistry and Biology

“…The broad toolkit of programmable oligomeric structures makes DNA and RNA invaluable scaffolds. [44] Colocalization of enzymes in a metabolic pathway can improve reaction efficiency by increasing the effective molarity of intermediate (see section 2, above) and, if the proteins are close enough, intermediate transfer is even more efficient as diffusion is dimensionally restricted along the protein hydration shells. [45] …”

DNA‐gesteuerte Synthese und Bioaktivität proapoptotischer Peptide

“…Diese Nukleinsäure-kodierte Information könnte genutzt werden, um molekulare Therapien selektiv auf erkrankte Zellen oder Gewebe zu richten. Ein interessanter Ansatz würde krankheitsspezifische Nukleinsäuresequenzen dazu nutzen, die Bildung oder Freisetzung von Wirkstoffmolekülen auszulö-sen. [1] Kürzlich wurde gezeigt, dass Hybridisierungsprozesse von Nukleinsäuren die Freisetzung von Modellwirkstoffen wie pNitrophenol und Cumarin, [2] Biotin oder Benzoesäure [3] steuern können. Gothelf, Mokhir et al führten die DNASteuerung der Bildung von Singulettsauerstoff durch Pyropheophorbid ein.…”

Nucleic Acid Templated Reactions for Chemical Biology

“…Bioorthogonal reactions catalyzed by spatial proximity and photoinduction can be used to trigger the release of prodrugs upon interaction with unique or overexpressed RNA or DNA sequences. Winssinger and co‐workers developed a para ‐azidobenzyl‐based immolative linker for the uncaging of functional molecules (Figure a).…”