Novel synthesis of a pentadentate ligand for designing protein-based artificial enzyme mimics

ORGN 520

Priya P. Joshi, David M. Weber, and Christin T. Choma. Department of Chemistry, Rensselaer Polytechnic Institute, 110 8th street, Troy, NY 12180
In this presentation, we demonstrate the novel synthesis of a pyridine-based pentadentate ligand for covalent incorporation into GCN4-p1-LI, a four-helix bundle composed of four identical peptides. The ligand, N4Py, is synthesized with four methylene spacers using a convergent strategy. The required spacers and functionalities are incorporated into the building blocks before the synthesis of the core of the ligand. The tethering of the ligand to the peptides is accomplished through four disulfide bonds. In order to overcome the possible problem of introducing the 'thiol' functionalities after the preparation of the N4Py framework, the required modification is achieved during the synthesis of the building blocks. The 'thiol' moieties are protected throughout the synthesis and deprotected once the N4Py scaffold is constructed. Physical-chemical characterization of the ligand-protein complex is proceeding.