Synthesis and UV hybridization studies of mixed-sequence pyrrolidine-amide oligonucleotide mimics (POM)

ORGN 605

Adam P. O'Rourke, adam.o'rourke@postgrad.manchester.ac.uk, Roberta J. Worthington, Jordi Morral, and Jason Micklefield. School of Chemistry, The University of Manchester, Faraday Tower, Sackville Street, Manchester, United Kingdom

Pyrrolidine-amide Oligonucleotide Mimics (POM) were designed to be configurational and conformational mimics of natural nucleic acids. They differ structurally from native nucleic acids in two ways; they have a pyrrolidine ring in place of the furanose sugar, and an amide moiety instead of a phosphodiester linkage. It is anticipated that a proportion of the pyrrolidine nitrogens will be protonated at physiological pH, making the backbone cationic.

POM binds with very high affinity to complementary single stranded RNA and DNA, with a kinetic preference for RNA over DNA. These properties give POM potential therapeutic and diagnostic applications.

The focus of our group's attention is threefold:

  • synthesis of the four POM monomers (T, CCbz, ACbz and GCbz)
  • solid-phase synthesis of mixed-sequence oligomers
  • UV melting and isothermal calorimetry studies