Oligonucleotides containing a nucleotide analog with an ethynylfluorobenzene as nucleobase surrogate

A Nucleobase Analogue that Pairs Strongly with Adenine

“…The instability of such species can be avoided when replacing a natural deoxynucleoside with a C‐nucleoside, so that a neutral and more stable glycosidic bond arrangement results. We have previously reported a 2‐ethynyl derivative of difluorotoluene ( 2 ), an isostere of thymidine,14 in the form of ethynylfluorobenzene nucleoside 3 , and we were able to show that it pairs more strongly with adenine when incorporated in an oligonucleotide than its fluoro counterpart 2 15. Still, the overall base pairing strength of 3 was considerably weaker than that of natural thymidine, as evidenced by a depression in the UV‐melting point of a dodecamer duplex by 12.7 °C, compared with the natural T‐containing duplex.…”

A Nucleobase Analogue that Pairs Strongly with Adenine

“…[24] It is also noteworthy how different the pairing properties of E are from those of difluorotoluene (F, Figure 1). Whereas F causes a drop in the melting point by 18 8C in a dodecamer duplex [15] and a DT m for a mismatched base facing it of less than 3 8C, [15,25] E causes a melting point increase of 2.6-5.8 8C per residue in perfectly matched duplexes, and a single mismatch depresses the T m by 14.5-19.8 8C (Table 2).…”

“…We have previously reported a 2-ethynyl derivative of difluorotoluene (2), an isostere of thymidine, [14] in the form of ethynylfluorobenzene nucleoside 3, and we were able to show that it pairs more strongly with adenine when incorporated in an oligonucleotide than its fluoro counterpart 2. [15] Still, the overall base pairing strength of 3 was considerably weaker than that of natural thymidine, as evidenced by a depression in the UV-melting point of a dodecamer duplex by 12.7 8C, compared with the natural T-containing duplex. Herein, we present 6-ethynylpyridone C-nucleoside 4, which combines the hydrogen bonding capabilities of T at the 3-and 4-positions with the ability of an ethynyl substituent to engage in stacking and van der Waals interactions.…”

“…[21] After detritylation, standard coupling cycles completed the chain assembly, which was followed by conventional deprotection and HPLC purification, yielding oligodeoxynucleotide 15, whose sequence was chosen to allow for comparison with other C-nucleosides. [15,22] Additionally, we prepared self-complementary oligonucleotide 16, whose duplex (16) 2 contains two residues of the ethynylpyridone (E).…”

Synthesis and applications of fluorinated nucleoside analogues

“…Griesang and Richert synthesized oligonucleotides containing a nucleotide analogue with an ethynyl fluorobenzene as a nucleobase surrogate [64]. Modified analogues of nucleobases may engage in duplex stabilizing interactions by forming additional hydrogen bonds, by binding via the major or the minor groove, or by offering additional surface sites for stacking.…”