Diastereoselective reversible C-C bond exchange of oxindole-thiazolidienediones for dynamic combinatorial chemistry.

We herein describe a diastereoselective aldol exchange involving isatins and thiazolidinediones, providing oxindolyl-thiazolidienediones in aqueous media at pH 6. This equilibrium can also be achieved with oxindole exchange as well as cross-exchange within reasonable timescales. These metal and organic catalyst free reversible reactions provide a unique opportunity for the evolution of dynamic combinatorial libraries (DCLs) for target directed dynamic combinatorial chemistry (DCC) and system chemistry.

Thiazole Containing PNA Mimic Regulates c-MYC Gene Expression through DNA G-Quadruplex.

Peptide nucleic acids (PNAs), besides hybridizing to complementary DNA and RNAs, bind and stabilize DNA secondary structures. Herein, we illustrate the design and synthesis of PNA-like scaffolds by incorporating five-membered thiazole rings as modified bases instead of nucleobases and their subsequent effects on gene regulation by biophysical and in vitro assays. A thiazole-modified PNA trimer selectively recognizes c-MYC G-quadruplex (G4) DNA over other G4s and duplex DNA. It displays a high stabilization potential for the c-MYC G4 DNA and shows remarkable fluorescence enhancement with the c-MYC G4. It is flexible enough to bind at 5' and 3' ends as well as in the groove region of c-MYC G4. Furthermore, the PNA trimer easily permeates the cellular membrane and suppresses c-MYC mRNA expression in HeLa cells by targeting the promoter G4. This study illuminates modified PNAs as flexible molecular tools for selective targeting of noncanonical nucleic acids and modulating gene function.