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Targeting DNA G-quadruplex structures with pyrazolo[3,4-d]pyrimidine guanine PNA oligomers

Wednesday, October 10, 2012 — Poster Session II

Noon – 2:00 p.m

Natcher Conference Center, Building 45




  • E.A. Englund
  • M.I Onyshchenko
  • C.M. Micklitsch
  • R.D. Neumann
  • I.G. Panyutin
  • D.H. Appella


Peptide Nucleic Acids (PNAs) are versatile nonnatural nucleic acid mimics with a pseudo peptide backbone used in lieu of sugar-phosphates. Although PNA oligomers bind natural nucleic acids with high affinity and selectivity, their application is limited by synthetic efficiency, solubility and non-specific interactions. The use of guanine-rich sequences is particularly precarious because of their tendency to aggregate and interact nonspecifically through Hoogsteen-face hydrogen bonding. In our research, we have developed and employed a series of Boc-protected PNA monomers containing pyrazolo[3,4-d]pyrimidine guanine (PPG) suitable for solid-phase peptide synthesis. PNA oligomers with PPG residues demonstrated reduced aggregation and improved target specificity. We used PPG-rich PNA oligomers to probe naturally occurring for DNA sequences that can be induced to form guanine quadruplexes. Regulating genes through targeting specific sequences of DNA and RNA is an attractive application for nucleic acid mimics; however, targeting the secondary structures of nucleic acids could provide greater specificity.

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