Deoxynucleic Guanidine/Peptide Nucleic Acid Chimeras:  Synthesis, Binding and Invasion Studies with DNA

Abstract

A fully automated solid-phase synthetic procedure for incorporation of positively charged guanidinium linkages into otherwise neutral PNA sequences has been employed. These DNG/PNA chimeras form [(DNG/ PNA) 2 ‚DNA] triplexes upon binding to single strand or duplex DNA (with accompanying D-loop for the latter). The [(DNG/PNA) 2 ‚DNA] triplexes of DNG/PNA T 10 , with DNA dA 10 , are more stable than DNA‚ DNA triplexes [(T 10 ) 2 ‚dA 10 ]. The binding of DNG/PNA chimera with guanidinium linkages on both ends, with single strand length-matched complementary DNA under thermal melt conditions and with longer double strand DNA under isothermal conditions is sequence specific. The association process of DNG/PNA chimera with single strand DNA and strand invasion of longer ds-DNA is faster than the association of PNA, with the same DNA targets, as evident by thermal hysteresis and gel retardation under isothermal conditions. The sequence specific and faster strand invasion of DNG/PNA may extend the potential utility of PNA in diagnostics, biomolecular probes, and antisense/antigene therapeutics.

Quadruplex-Forming Oligonucleotides as Tools in Anticancer Therapy and Aptamers Design: Energetic Aspects

“…Further, PNA-DNA chimeras possess interesting biological properties as antisense agents [110] and also as decoys against NF-kB transcription factors [111,112]. Moreover, PNA-DNA chimeras have been shown to form triple helix structure [113][114][115].…”

REACTION OF N3-BENZOYL-3′,5′-O-(DI-TERT-BUTYLSILANEDIYL)URIDINE WITH HINDERED ELECTROPHILES: INTERMOLECULAR N3To 2′-OPROTECTING GROUP TRANSFER

“…The yield was 71%. IR (NaCl) 1747 (s), 1708 (s), 1678 (s) cm À 1 ; 1 H NMR (300 MHz, CDCl 3 (6). N 3 -Benzoyl-3 0 ,5 0 -O-(di-tert-butylsilanediyl)uridine 2 (245 mg, 0.5 mmol) and 1-bromo-2-ethylbutane (140 mL, 1.0 mmol) were dissolved in CH 3 CN (1.0 mL) with n-Bu 4 NI (37 mg, 0.1 mmol) as catalyst.…”

“…[2] More recently, the polyanionic backbone of traditional antisense nucleotides has been recognized as a disadvantage in intracellular uptake and the cause of limited affinity to targeted natural oligonucleotide fragments. [3] The negatively charged structure is also sensitive to nucleases. [3] Replacement of the nucleotide backbone has led to PNA (peptide nucleic acid) technology and more radical structures such as positively charged guanidinium linkages.…”

“…[3] Replacement of the nucleotide backbone has led to PNA (peptide nucleic acid) technology and more radical structures such as positively charged guanidinium linkages. [3][4][5] Currently there are also groups developing oligonucleotides with 3 0 -3 0 -internucleotide linkages at the end of the sequence, to achieve resistance to exonucleases. [6] A very large number of modified species have been produced and characterized by the anti-sense and gene therapy enterprises.…”

Synthesis and Structural Characterization of PNA‐DNA Quadruplex‐Forming Chimeras

“…[12] Furthermore, some types of PNA-DNA chimeras have also been shown to form triple helix structures. [13,14] In an effort to expand the versatility of these molecules, we have been investigating the ability of PNA-DNA chimeras to form quadruplex structures. In fact, the presence of a PNA tract should enhance the exonuclease stability and hence the biological activity of these structures, the relevance of which has been dramatically increased by their presence in telomeric sequences and in several biologically active aptamers, as well as by finding of a number of quadruplex-binding proteins.…”