Nucleosides with Transposed Base or 4′-Hydroxymethyl Moieties and Their Corresponding Oligonucleotides

Abstract

This review focuses on 4'-hydroxymethyl- or nucleobase-transposed nucleosides, nucleotides, and nucleoside phosphonates, their stereoisomers, and their close analogues. The biological activities of all known 4'-hydroxymethyl- or nucleobase-transposed nucleosides, nucleotides, and nucleoside phosphonates as potential antiviral or anticancer agents are compiled. The routes that have been taken for the chemical synthesis of such nucleoside derivatives are described, with special attention to the innovative strategies. The enzymatic synthesis, base-pairing properties, structure, and stability of oligonucleotides containing nucleobase- or 4'-hydroxymethyl-transposed nucleotides are discussed. The use of oligonucleotides containing nucleobase- or 4'-hydroxymethyl-transposed nucleotides as small oligonucleotide (e.g., human immunodeficiency virus integrase) inhibitors, in applications such as antisense therapy, silencing RNA (siRNA), or aptamer selections, is detailed.

Thermodynamic Insights of Base Flipping in TNA Duplex: Force Fields, Salt Concentrations, and Free-Energy Simulation Methods

“…(2) The enzymatic and nonenzymatic polymerization of the TNA nucleotide is possible due to this cross-pairing with other polynucleotides. [17][18][19][20][21][22][23] (3) TNA is often assumed to be a good predecessor of RNA, 24,25 but the chemical stability of TNA is higher, and the number of reactive groups is smaller, which leads to fewer side reactions, and thus, more faithful copying. (4) Regioselectivity is no longer a problem due to the presence of only two hydroxyl groups in each sugar moiety of the TNA polymer.…”

Synthesis of a Threosyl‐C‐nucleoside Phosphonate

“…[6] Besides, α-L-threose nucleosides containing a four-carbon Lthreosyl sugar ring have been investigated for different purposes. [7] In particular, they are the building blocks of threose nucleic acid (TNA), which is an artificial genetic polymer able to form thermally stable self-duplexes by Watson-Crick base pairing as well as hybrids with complementary DNA and RNA strands. [8] Its capacity to fold into functional tertiary structures able to bind targets with high affinity and specificity has also been demonstrated.…”

Ferrocenyl GNA Nucleosides: A Bridge between Organic and Organometallic Xeno‐nucleic Acids

“…The arrows in Figure tentatively represent gradual structural changes on going from the glycol nucleic acid (GNA) nucleoside, followed by flexible nucleic acid (FNA) nucleosides through canonical thymidine nucleosides and finally to their more structurally distant congeners such as arabino nucleic acid (ANA), 2′‐fluoro‐arabino nucleic acid (FANA), and α‐ l ‐threofuranose nucleic acid (TNA) nucleosides. Branches consist of aminopropyl nucleic acid (APNA) nucleosides, d ‐threoninol nucleosides, isonucleosides (INA) and locked nucleic acid (LNA) nucleosides . Branched from DNA are the homo‐DNA, hexitol nucleic acid (HNA), cyclohexene nucleic acid (CeNA) and morpholino nucleic acid nucleosides .…”