Synthesis of Novel Disulfide Linked Peptide Nucleic Acid (PNA) Monomers

Peptide Nucleic Acids (PNAs) are pseudopeptides that utilize the same nucleobases as DNA and RNA that permits them to be incorporated in Watson-Crick base pairing to form homogeneous (PNA/PNA) or heterogeneous (PNA/DNA or PNA/RNA) duplexes. As a result, PNAs can function as either antigene (DNA transcription blockers) or antisense (RNA translation blockers) chemical agents. To do this, PNAs must reach the cytoplasm in order to hybridize with their respective DNA or RNA target. Unfortunately, this proves to be challenging as PNAs do not readily penetrate cell membranes. In efforts of addressing this issue, we proposed developing PNA/PNA duplexes consisting of an antisense probe duplexed with a temporary “delivery” PNA strand that is held together by disulfide bonds. Due the temporary PNA strand being decorated in chemical markers and cell penetrating peptides, the cell is “tricked” cell into taking the antisense PNA across the cell membrane and into the cytoplasm to reach its desired target. Specifically, our research is focused on synthesizing novel PNA monomers with different synthetic modifications near the disulfide bond. Ultimately, these monomers will be incorporated into the backbone of the temporary “delivery” PNA strand and assessed for any consequences they may have on cleavage efficiency