Modular Assembly Using Sequential Palladium Coupling Gives Easy Access to the SMoC Class of Cellular Transporters
A. Rebstock, C. Visintin, Elisabetta Leo
Jul 21, 2008
Citations
10
Citations
Journal
ChemBioChem
Full text
Semantic Scholar
Key Takeaway Key Takeaway: The SMoC class of cellular transporters, which can effectively inhibit DNA replication in various cell types, can be efficiently synthesized using sequential Pd0 coupling chemistry.
Abstract
The transducing ability of the third helix of transcription factor homeodomains is effectively mimicked by a biphenyl system displaying guanidine groups. The biphenyl class of small molecule carriers (SMoCs) can carry biomolecules into a wide variety of cell types. A “combinatorial” approach to the synthesis of SMoCs is described using sequential Pd0 coupling chemistry to assemble the molecules from highly functionalized building blocks. SMoCs coupled to the DNA licensing repressor protein geminin can inhibit DNA replication in vitro. We conducted a structure–activity investigation utilizing a range of SMoC–geminin conjugates and demonstrate that both electrostatic and structural features are important for efficient uptake and functional activity. The best analogue was more efficient than either (Arg)4 or (Arg)8 linked to geminin. Effective inhibition of DNA synthesis was achieved in fibroblasts and osteosarcoma cell lines.