Oligonucleotide Analogues with Integrated Bases and Backbone

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The A*[s]U ( * ) dinucleosides 1 and 2 form thermoreversible gels in organic solvents. The basis of the gelation is the formation of linear aggregates by base pairing following desolvation of the nucleobases. This is evidenced by the absence of gel formation by the C(6)-deaminated analogue 3 of 1, the correlation of gelation with the anti-conformation, as preferred for 1, and the temperature-, concentration-, and timedependent CD spectra. The gels were also characterized by the minimum gelation concentration, the gel -sol transition (melting) temperature, and rheological properties.

mentioning

confidence: 94%

Oligonucleotide Analogues with Integrated Bases and Backbones. Part 19.

Bogliotti¹,

Ritter²,

Hebbe³

et al. 2008

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“…) See[27] for a similar observation for duplexes of U*[s]U* dinucleosides. 7 ) There are two NH signals at higher concentration that coalesce at lower concentration.…”

mentioning

confidence: 62%

“…The homoassociation of lipophilic cytidines in CHCl 3 was studied by IR [22], Raman [23], and 1 H-NMR spectroscopy [24], and by calorimetry [25]. An association constant K ass ¼ 40 -42 m À1 at 258 was determined, assuming a 1 : 1 association, with ÀDH8 ¼ 4.9 kcal/mol 4 ) [23] [24], similar to the self-association of adenosines and uridines in CHCl 3 [26] [27]. Ab initio calculations of the C i -symmetric CC base pair [28] evidence a length of 2.05 for the NH ··· N H-bond and a stabilisation energy of 17.35 kcal/mol for one base pair in the gas phase.…”

mentioning

confidence: 98%

Oligonucleotide Analogues with Integrated Bases and Backbone. Part 27

Herdeis

Bernet

Augustine

et al. 2011

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The (chloromethyl)cytidine 7 was obtained from alcohol 4 that was synthesized from the protected cytidine 3 by C(6)-formylation and reduction. Thioacetate 10 was obtained from the cytidine 2, and thioacetate 8 from a Mitsunobu reaction of alcohol 6. The thiomethylene-linked dinucleoside 11 was synthesized by thioether formation between the 6-(chloromethyl)cytidine 7 and the thiolate generated by S-deacetylating and N-debenzoylating the cytidine-5'-thioacetate 10. Dinucleoside 11 was desilylated to 12, and fully deprotected to 13. Similarly to 11, the C(6)-substituted analogue 14 was obtained from 7 and the C(6)-substituted 8. Stepwise deprotection of 14 provided 15 -17, and complete deprotection gave 18. The thioacetylated and N-benzoylated dinucleoside 21 was obtained from the methanesulfonate 9 and the thiolate that was generated from thioacetate 8. Similarly, 7 and 8 yielded 19 that was transformed into the methanesulfonate 20. The tetranucleoside 23 was synthesized from the methanesulfonate 20 and the thiol derived from 21. It was debenzoylated to 23 and completely deprotected to 24.The partially protected dinucleosides 11, 14, and 15, and the tetranucleoside 23 pair strongly in CDCl 3 . The crystal structure of 11 · MeOH shows the formation of an antiparallel cyclic duplex possessing nearly orthogonal base pairs due to MeOH acting as H-acceptor from one base pair and Hdonor to the other base pair. A large distance of ca. 6 between the base pairs of the cyclic duplexes was predicted by Maruzen modeling. It is corroborated by the absence of base stacking in CHCl 3 solution of the duplexes formed by the (self-complementary) dinucleosides 11, 14, and 15, as evidenced by a weak temperature dependence of the CD spectra. The association constants for 11, 14, 15, and 23 were calculated from the concentration dependence of the chemical shift of H 2 NÀC(4). No concentration dependence of the H 2 NÀC(4) signals was observed for solutions of 23 in CDCl 3 , (D 6 )acetone, CD 3 CN, (D 8 )THF, (D 5 )pyridine, and CDCl 3 /(D 6 )DMSO 4 : 1. As a consequence of the strong association, the association constant for 23 had to be determined in CD 3 CN/(D 6 )DMSO 4 : 1. The temperature dependence of the CD spectra of the fully deprotected 18 und 24, but not of 13, in H 2 O is rationalized by base stacking of the hydroxymethylated cytosine moieties that associate by intermolecular H-bonds of HOCH 2 ÀC(6/I) to an acceptor of unit I. The 1 H-NMR spectrum of 18 and 24, but not of 13, shows a 9 : 1 mixture of the monoplex and the base-stacked duplex.

“…Four building blocks (Scheme 1) are required for the linear synthesis of a tetramer (or a higher oligomer). Two building blocks corresponding to the terminal unit I (Schemes 2 and 3) possess a C(5')SH and a protected hydroxymethyl group at C(6) or C (8), and act exclusively as nucleophile. Two building blocks corresponding to the internal units II and III of the tetramer possess a protected thiol and a halogenomethyl group, and act in sequence as electrophile and as nucleophile.…”

Section: In Continuing the Exploration Of Thiomethylene-linked Onibs mentioning

confidence: 99%

“…The polyol 27 is insoluble in CDCl 3 , and the NMR spectra were recorded in (D 6 )DMSO. The NMR data compiled in Tables 6 -9 [8]). These chemical shifts evidence an equilibrium between the monoplex and linear U · U duplexes, although a small contribution of linear and cyclic duplexes possessing Hoogsteen-type base pairing cannot be excluded.…”

Section: In Continuing the Exploration Of Thiomethylene-linked Onibs mentioning

confidence: 99%

Oligonucleotide Analogues with Integrated Bases and Backbone. Part 22

Bernet

Johar

Ritter

et al. 2009

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The tritylated and silylated self-complementary A*[s]U*[s]A*[s]U* and U*[s]A*[s]U*[s]A* tetramers 18 and 24, linked by thiomethylene groups (abbreviated as [s]) between a nucleobase and C(5') of the neighbouring nucleoside unit were prepared by a linear synthesis based on S-alkylation of 5'thionucleosides by 6-(chloromethyl)uridines, 7 or 10, or 8-(chloromethyl)adenosines, 12 or 15. The tetramers 18 and 24 were detritylated to the monoalcohols 19 and 25, and these were desilylated to the diols 20 and 26, respectively. The association of the tetramers 18 -21 and 24 -26 in CDCl 3 or in CDCl 3 / (D 6 )DMSO 95 : 5 was investigated by the concentration dependence of the chemical shifts for HÀN (3) or H 2 NÀC(6). The formation of cyclic duplexes connected by four base pairs is favoured by the presence of one and especially of two OH groups. The diol 20 with the AUAU sequence prefers reverse-Hoogsteen, and diol 26 with the UAUA sequence Watson -Crick base pairing. The structure of the cyclic duplex of 26 in CDCl 3 at 28 was derived by a combination of AMBER* modeling and simulated annealing with NMRderived distance and torsion-angle restraints resulting in a Watson -Crick base-paired right-handed antiparallel helix showing large roll angles, especially between the centre base pairs, leading to a bent helix axis.