Oligonucleosides with a Nucleobase-Including Backbone, Part 7

Bhardwaj, Punit Kumar; Vasella, Andrea

doi:10.1002/1522-2675(200203)85:3<699::aid-hlca699>3.0.co;2-n

Cited by 15 publications

(4 citation statements)

References 11 publications

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“…We had hoped that the sterically undemanding ethynyl substituent might be compatible with a sufficient population of the anti conformation to allow base pairing. However, conformational analysis of the dimer 5 demonstrated a persistent hydrogen bond between the propargylic hydroxy group and N(3) of the same monomeric unit that is only compatible with a syn conformation [43]. In keeping with this observation, fully deprotected tetramers did not pair in MeOH, while the protected tetramer 6 associated in CDCl 3 [41] [44].…”

Section: Resultsmentioning

confidence: 89%

Oligonucleosides with Integrated Backbone and Base: Foldamers with a Novel Architecture

Vasella¹

2005

Chimia

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Dinucleoside and tetranucleoside analogues with integrated backbone and nucleobase represent a novel type of oligonucleotide foldamers. They are characterized by a linker between C(5ʹ) of one nucleoside moiety and C(8) of an adjacent adenosine, or C(6) of an adjacent uridine. Solutions in chloroform or chloroform/DMSO of these partially protected di-, or tetranucleoside analogues associate. The strength of the association depends on the nature of the linker, the presence, or absence of a hydroxymethyl group on the terminal nucleobase, other protecting groups, and intramolecular hydrogen bonds. The thiomethylene-linked dimers were studied in detail; one of them associates strongly enough that a melting temperature can be determined, evidencing base stacking in chloroform solution. Some dimers form organogels. Two 2ʹ,3ʹ-O-isopropylidene protected self-complementary tetramers were prepared. Their duplexes are conformationally homogeneous. One of the tetramers was characterised in detail; it associates via hydrogen bonds of the Watson-Crick type to form a partial A-type helix with all bases in a synconformation and a rather large twist angle. Also studied were di-and tetranucleotide analogues possessing an all-carbon linker; they were derived from (hydroxy)propynylene linked dimers by deoxygenation, partial reduction to the (E)-and (Z)-propenylene linked analogues, and further hydrogenation to propanylene-linked analogues. The propargylic hydroxy group forms an intramolecular hydrogen bond to N(3) of the adenine moiety of the same unit; the resulting conformers associate weakly. Deoxygenation leads to foldamers that associate much more strongly. A (Z)-propenylene-linked dimer also associates strongly, its (E) isomer less so, and the propanylene-linked analogues associate weakly. The results show that backbone-base integration defines a novel structural relation between backbone and nucleobases that favours selective pairing and leads to oligonucleotide foldamers.

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Section: Resultsmentioning

confidence: 89%

Oligonucleosides with Integrated Backbone and Base: Foldamers with a Novel Architecture

Vasella¹

2005

Chimia

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“…The estimated twist angles are 608 between the terminal and 458 between the centre base pairs (Fig. 9, d) 9 ).…”

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

confidence: 93%

“…Adding increasing amounts of (D 6 )DMSO to CDCl 3 solutions of self-complementary dinucleosides shifts the monoplex > duplex equilibrium progressively in favour of the (solvated) monoplex [9]. Upon addition of 50% of (D 6 )DMSO, d(HÀN(3/a)) and d(HÀN(3/b)) of 19 decrease from 13.70 to 10.70, and from 12.53 to 10.59 ppm, respectively.…”

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

Helvetica Chimica Acta

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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.

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“…2 Modeling suggested that an anti conformation of these analogues is a prerequisite for pairing, whilst NMR analysis of an adenosine dimer showed that a syn conformation is preferred. 3 Modeling studies also suggested that oxymethylene-bridged oligomers (Fig. 2), should pair in the syn conformation (Watson-Crick type hydrogen bonding), so far only known to occur in Z-DNA.…”

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confidence: 99%