Thermodynamic and biological evaluation of a thrombin binding aptamer modified with several unlocked nucleic acid (UNA) monomers and a 2′-C-piperazino-UNA monomer

Dissecting the chemical interactions and substrate structural signatures governing RNA polymerase II trigger loop closure by synthetic nucleic acid analogues

“…In order to dissect the individual contribution of these two factors, we employed two ATP analogues: unlocked ATP (UNA-ATP) and locked ATP (LNA-ATP) (Figure 3A) (24,35,43–46). UNA-ATP is a nucleic acid analogue consisting of all of the functional groups of natural NTP but lacking a bond between C2 and C3 in the sugar ring.…”

The effect of l-thymidine, acyclic thymine and 8-bromoguanine on the stability of model G-quadruplex structures

“…TBA variants with GNAT modifications showed similar TDS than TBA. Based on these data we can conclude that, although GNAT contains a short backbone, it has a similar behavior as UNA derivatives [12,34]. Both derivatives increase TBA stability in position 7 [12].…”

“…Both derivatives increase TBA stability in position 7 [12]. In addition , 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 multiple UNA modifications in TBA were also studied [34]. Similar to our work with GNAT, a position-dependent effect was observed being position 7, 3 and 12 the most tolerant in the TBA stability.…”

Polyvalent nucleic acid aptamers and modulation of their activity: a focus on the thrombin binding aptamer

“…Some researchers have exploited non-natural modifications of the nucleobases (Krawczyk et al, 1995;He et al, 1998a;Marathias et al, 1999;López de la Osa et al, 2006;Mendelboum Raviv et al, 2008;Nallagatla et al, 2009;Goji & Matsui, 2011), which included: 1) guanines modified with hydrophobic substituents in the N 2 and C 8 positions; 2) 6-thio-, 3) 8-amino-, 4) iso-, and 5) 8-bromo-guanine modifications; and 6) thymine with 4-thio-uracil substitutions. Other research groups modified the nucleotide backbone of TBA 15 by introducing valuable surrogates replacing the natural phosphodiester linkages, such as: 1) neutral formacetal groups (He et al, 1998b), 2) phosphorothioate linkages (Saccà et al, 2005;Pozmogova et al, 2010;Zaitseva et al, 2010), 3) 3′-3′ or 5′-5′ phosphodiester bonds (Martino et al, 2006;Esposito et al, 2007;Pagano et al, 2008;Russo Krauss et al, 2011), and 4) methylphosphonate bonds (Saccà et al, 2005), or the nucleoside moieties, with insertion within the backbone of: 5) 2′-deoxy-2′-fluoro-D-arabinonucleotides (2′F-araN) (Peng & Damha, 2007), 6) locked-nucleic acids Bonifacio et al, 2008), 7) unlocked nucleic acids (UNA) (Agarwal et al, 2011;Jensen et al, 2011;Pasternak et al, 2011), and 8) acyclic thymine nucleoside (Coppola et al, 2008) residues. Most of these chemical modifications do not result into relevant improvements in the anticoagulant properties of TBA, even if in some reports an increase of the overall stability of the G-quadruplex structure and/or of the affinity for thrombin is registered.…”