Synthesis and Structural Properties of New Oligodeoxynucleotide Analogues Containing a 2′,5′‐Internucleotidic Squaryldiamide Linkage Capable of Formation of a Watson−Crick Base Pair with Adenine and a Wobble Base Pair with Guanine at the 3′‐Downstream Junction Site

Abstract

Keywords: DNA / Hybridization / Hydrogen bonds / Phosphate mimic / Squaric acid / WatsonϪCrick base pair / Wobble base pair A TpT dimer analogue (U 2Ј sq 5Ј T), in which the 3Ј-5Ј phosphodiester linkage was replaced by a 2Ј-5Ј squaryldiamide linkage and the 5Ј-upstream T was replaced by a 3Ј-deoxyuridine, was synthesized in almost quantitative yield from diethyl squarate. This new dimer structural motif was designed to eliminate the squaryldiamide skeleton-induced overall strain in T 3Ј sq 5Ј T, previously incorporated into DNA fragments as a new TpT mimic, through the change in the connection mode from the 3Ј-5Ј linkage to a 2Ј-5Ј linkage. Spectral analyses of U 2Ј sq 5Ј T suggest that the overall structure of this dimer mimic is basically similar to that of TpT. A DNA 10mer 5Ј-d(CGCAU 2Ј sq 5Ј TAGCC)-3Ј incorporating this dimer was synthesized. From the CD analysis, it turned out that the overall structure of a DNA duplex of 5Ј-

Chemical Modification of Oligonucleotides for Therapeutic, Bioanalytical and other Applications

“…[6] Nakamura and co-workers were more successful in replacing the phosphodiester backbone of DNA with a TL DNA (7). A decamer homothymine TL DNA oligomer was assembled by solid phase chemistry by using a thymidine monomer that was modified to contain both a 5'-trimethylsilyl-protected acetylene and a 3'-deoxyazido moiety.…”

Synthesis and Properties of New Nucleotide Analogues Possessing Squaramide Moieties as New Phosphate Isosters

“…[4] Recently, we have proposed similarities in the electronic structures of squaric acid and phosphoric acid, and have reported the synthesis of artificial DNAs containing 3Ј-5Ј and 2Ј-5Ј squaryl dimide linkages, which displayed an unusual bent structure and G-T mismatch stabilization, respectively. [5,6] The potential of squaric acid as a phosphate mimic has also been proposed by Seto and coworkers [7] in the development of protein tyrosine phosphatase inhibitors. we also synthesized 3Ј,5Ј-cyclic nucleotide analogues from the 3Ј,5Ј-diazidonucleoside derivatives.…”

An analytical method for prohexadione in Chinese cabbage and apple

“…The biological activity of squaramides relies on specific structural features; the squaramide1 motif provides a planar aromatic2 framework equipped with two adjacent carbonyl acceptor groups and two NH amide‐type donor sites, capable of establishing multiple hydrogen bond interactions 3–6. A number of squaramides are currently under investigation for biological effects such as bioisosteric substitution of phosphate groups in modified oligodeoxynucleotides7, 8 and of guanidines in compounds that show activity as potassium channel openers 9–11. In addition, squaramide‐based compounds target certain CXC‐type chemokine receptors12–14 and are involved in ligands designed for receptor‐binding inhibition of enterotoxins 15–17.…”