title: Synthesis and characterization of conformationally preorganized, (R)-diethylene glycol-containing γ-peptide nucleic acids with superior hybridization properties and water solubility.
abstract: Developed in the early 1990s, peptide nucleic acid (PNA) has emerged as a promising class of nucleic acid mimic because of its strong binding affinity and sequence selectivity toward DNA and RNA and resistance to enzymatic degradation by proteases and nucleases; however, the main drawbacks, as compared to other classes of oligonucleotides, are water solubility and biocompatibility. Herein we show that installation of a relatively small, hydrophilic (R)-diethylene glycol ("miniPEG", R-MP) unit at the γ-backbone transforms a randomly folded PNA into a right-handed helix. Synthesis of optically pure (R-MP)γPNA monomers is described, which can be accomplished in a few simple steps from a commercially available and relatively cheap Boc-l-serine. Once synthesized, (R-MP)γPNA oligomers are preorganized into a right-handed helix, hybridize to DNA and RNA with greater affinity and sequence selectivity, and are more water soluble and less aggregating than the parental PNA oligomers. The results presented herein have important implications for the future design and application of PNA in biology, biotechnology, and medicine, as well as in other disciplines, including drug discovery and molecular engineering.
authors: Department of Chemistry and Center for Nucleic Acids Science and Technology (CNAST), Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States.
authors: Bichismita
authors: B
authors: Sahu
authors: Iulia
authors: I
authors: Sacui
authors: Srinivas
authors: S
authors: Rapireddy
authors: Kimberly J
authors: KJ
authors: Zanotti
authors: Raman
authors: R
authors: Bahal
authors: Bruce A
authors: BA
authors: Armitage
authors: Danith H
authors: DH
authors: Ly
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