Abstract:

The ability to efficiently hydrolyze nucleic acids in a biomimetic non-destructive process with high selectivity has become important because one can find many applications in structural design of new probes and drug development. This molecular recognition is a common feature in biological systems, where some functional groups form supramolecular systems by non-covalent interactions. For example, the guanidinium group present in the active site of the Staphylococcus nuclease is used to recognize the phosphodiester group, accelerating its hydrolysis. Recently, our group has synthesized the alkaloid tetrahydro-_-carboline (S)-(-)-trypargine (1) that presents a side chain at C1 with a terminal guanidine residue. Therefore, we decided to synthesize new derivatives of trypargine (2 and 3) in order to investigate their ability to recognize and trigger hydrolysis of phosphodiesters, such as DNA and RNA.