Electronic Thesis and Dissertation Repository


Master of Science




Hudson, Robert H.E.


Pseudo-complementary nucleobases are modified nucleobases which exhibit normal base pairing with unmodified complementary nucleobases; however, will not undergo stable base pairing with other pseudo-complementary nucleobases. The pseudo-complementary nature of these bases is of interest for the synthesis of pseudo-complementary peptide nucleic acid (pcPNA) oligomers, which are capable of binding targets in double-stranded DNA through a double duplex strand invasion. Until recently, pcPNAs were synthesized via Boc-based oligomerization chemistry which is currently less popular than the Fmoc-based strategy.

This research describes the development of a Fmoc protected thiouracil PNA monomer with an acid labile protecting group for use in standard SPPS. The synthesis uses an orthogonal protection strategy where the nucleobase is deprotected under standard acidic deprotection and resin cleavage conditions, while oligomerization occurs under basic conditions.