Manipulation of protein superstructures via the introduction of heterocyclic moieties

BIOL 60

Nicola McMillan, nimcmi@chem.gla.ac.uk, Department of Chemistry, University of Galsgow, Joseph Black Building, University Avenue, Glasgow, G12 8QQ, United Kingdom
The introduction of unnatural functional groups and new scaffolds into proteins is of interest but successful examples have been limited. In addition we have recently discovered a new type of heterocycle, di-hydro imidazo phenanthridinium (DIP), which is DNA interactive and cytotoxic.[1] The flexibility of the reaction methodology, allows access to a diverse library of DIP-based systems and we have been able to introduce the DIP moiety into protein superstructures. This is because the primary amines found on the lysine residues of proteins are ideal as starting materials for the formation of polyvalent DIPs, as the protein can be decorated with many DIP moieties providing a novel route to the post translational modification of proteins. We discuss the modification along with the structural changes introduced into the protein.

[1] Parenty, A. D. C.; Smith, L. V.; Pickering, A. L.; Long, D-L; Cronin, L. J. Org. Chem. 2004, 69, 5934-5946.