Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

Abramova, Tatyana V.; Belov, Sergey S.; Tarasenko, Yulia V.; Silnikov, Vladimir N.

doi:10.3762/bjoc.10.115

Cited by 13 publications

(9 citation statements)

References 24 publications

(34 reference statements)

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“…Recently, we developed methylenecarboxamide (glycine) morpholine (gM) nucleic acids analogues with the modified backbone . Their ability to form complexes with complementary DNA and RNA was shown previously .…”

Section: Introductionmentioning

confidence: 99%

Structure and Hybridization Properties of Glycine Morpholine Oligomers in Complexes with DNA and RNA: Experimental and Molecular Dynamics Studies

et al. 2019

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Methylenecarboxamide (glycine) morpholine oligomers (gMOs) with a modified backbone are new and promising nucleic acid analogues. In this work, a combination of circular dichroism spectroscopy, optical melting, and molecular dynamics simulations was used to investigate hybridization properties of gMOs, as well as the structure and dynamics of their tandem complexes with DNA and RNA. It was shown that the structure of nucleic acids in modified complexes is similar to that of the fully native analogues. The energies of binding and cooperative interactions at the helix−helix interface in the nick were determined experimentally and by computer simulation analysis. Here, we found for the first time, the possibility to determine and predict precisely the thermodynamic parameters of complementary complex formation using the original experimental and computer simulation approaches. It was shown that the use of simulation data in the explicit solvent and the molecular mechanics Poisson− Boltzmann (or generalized Born) surface area methods for the calculation of the hybridization enthalpy makes it possible to evaluate the thermal stability of DNA and gMO tandem duplexes with DNA or RNA with an unexpectedly high accuracy. We found that at high ionic strength and neutral pH, the observed thermal stability of the gMO/RNA tandem complex is similar to that of DNA/DNA and lower than that of gMO/DNA which is close to that of DNA/RNA.

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Section: Introductionmentioning

confidence: 99%

Structure and Hybridization Properties of Glycine Morpholine Oligomers in Complexes with DNA and RNA: Experimental and Molecular Dynamics Studies

et al. 2019

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“…One of them is based on the one-pot synthesis of 2 -azidomethylmorpholino nucleosides under the treatment of compounds 2A,G,C,U,T with Ph 3 P/CBrCl 3 /NaN 3 in dry dimethylformamide (DMF). After reduction of the N 3 -group and a full deblocation procedure, 2 -aminomethylmorpholino nucleosides were obtained in an overall yield of 39%-64% [46,64].…”

Section: Synthesis Of Adp Conjugates Containing Phosphoramide (P-n) Bondmentioning

confidence: 99%

“…We did not find any data concerning the synthesis of 2 -aminomethylmorpholino nucleosides 7IU, BrU, ClU containing 5-halosubstituited uracil or any modified heterocyclic base in the literature. Thus, at first, we tried to synthesize the azido derivative 6BrU following the one-pot procedure using Ph 3 P/CBrCl 3 /NaN 3 in dry DMF according to the published method [46]. However, our attempts failed.…”

Section: Synthesis Of Adp Conjugates Containing Phosphoramide (P-n) Bondmentioning

confidence: 99%

“…It was shown that some of those provided an inhibitory effect to the autopoly(ADP-ribosyl)ation of PARP-1; IC 50 of the most effective conjugate consisting of ADP and morpholino-glycine thymine nucleoside [46] was 41.5 ± 3.5 µM [45]. The combination of data from in silico models of PARP-1 with the NAD+-molecule [47] and the crystal structure of the CAT-∆HD domain of PARP-1 with the non-hydrolyzable NAD+ analog of BAD [38] suggests the requirement of conducting a rational searching for the details of mechanisms of action and specificity of new NAD+ analogs, being the conjugates of ADP and morpholino nucleosides.…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis and Molecular Modeling Study of Conjugates of ADP and Morpholino Nucleosides as A Novel Class of Inhibitors of PARP-1, PARP-2 and PARP-3

Sherstyuk

Ivanisenko

Zakharenko

et al. 2019

IJMS

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We report on the design, synthesis and molecular modeling study of conjugates of adenosine diphosphate (ADP) and morpholino nucleosides as potential selective inhibitors of poly(ADP-ribose)polymerases-1, 2 and 3. Sixteen dinucleoside pyrophosphates containing natural heterocyclic bases as well as 5-haloganeted pyrimidines, and mimicking a main substrate of these enzymes, nicotinamide adenine dinucleotide (NAD+)-molecule, have been synthesized in a high yield. Morpholino nucleosides have been tethered to the β-phosphate of ADP via a phosphoester or phosphoramide bond. Screening of the inhibiting properties of these derivatives on the autopoly(ADP-ribosyl)ation of PARP-1 and PARP-2 has shown that the effect depends upon the type of nucleobase as well as on the linkage between ADP and morpholino nucleoside. The 5-iodination of uracil and the introduction of the P–N bond in NAD+-mimetics have shown to increase inhibition properties. Structural modeling suggested that the P–N bond can stabilize the pyrophosphate group in active conformation due to the formation of an intramolecular hydrogen bond. The most active NAD+ analog against PARP-1 contained 5-iodouracil 2ʹ-aminomethylmorpholino nucleoside with IC50 126 ± 6 μM, while in the case of PARP-2 it was adenine 2ʹ-aminomethylmorpholino nucleoside (IC50 63 ± 10 μM). In silico analysis revealed that thymine and uracil-based NAD+ analogs were recognized as the NAD+-analog that targets the nicotinamide binding site. On the contrary, the adenine 2ʹ-aminomethylmorpholino nucleoside-based NAD+ analogs were predicted to identify as PAR-analogs that target the acceptor binding site of PARP-2, representing a novel molecular mechanism for selective PARP inhibition. This discovery opens a new avenue for the rational design of PARP-1/2 specific inhibitors.

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“…The synthesis of alcohol intermediates 3 was reported in 1993 by Summerton in a patent 26 and consisted in a "one-pot" oxidative ring-opening and reductive amination of the ribose sugar leading to the obtainment of the morpholino ring (Scheme 2). Several modifications of this procedure have been reported in the last years [27][28][29][30] . Here, we started from unprotected ribonucleosides, using the Summerton's procedure with different work up conditions.…”

mentioning

confidence: 99%

Nucleobase morpholino β amino acids as molecular chimeras for the preparation of photoluminescent materials from ribonucleosides

Bucci

Bossi²,

Erba

et al. 2020

Sci Rep

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Bioinspired smart materials represent a tremendously growing research field and the obtainment of new building blocks is at the molecular basis of this technology progress. In this work, colloidal materials have been prepared in few steps starting from ribonucleosides. Nucleobase morpholino β-amino acids are the chimera key intermediates allowing Phe–Phe dipeptides’ functionalization with adenine and thymine. The obtained compounds self-aggregate showing enhanced photoluminescent features, such as deep blue fluorescence and phosphorescence emissions.

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Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

Cited by 13 publications

References 24 publications

Structure and Hybridization Properties of Glycine Morpholine Oligomers in Complexes with DNA and RNA: Experimental and Molecular Dynamics Studies

Structure and Hybridization Properties of Glycine Morpholine Oligomers in Complexes with DNA and RNA: Experimental and Molecular Dynamics Studies

Design, Synthesis and Molecular Modeling Study of Conjugates of ADP and Morpholino Nucleosides as A Novel Class of Inhibitors of PARP-1, PARP-2 and PARP-3

Nucleobase morpholino β amino acids as molecular chimeras for the preparation of photoluminescent materials from ribonucleosides

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