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F Seela

Publications and source records attributed to F Seela.

At least 19 recordsLinked to original sources
PubMed2005

Synthesis of 5-aza-7-deazaguanine nucleoside derivatives as potential anti-flavivirus agents.

Coupling suitable sugars (D- or L-ribofuranose, 2' or 3-deoxysugar, branched sugars) with 2-aminoimidazo[1,2-a]-s-triazin-4-one was carried out using the different reaction conditions: 1) condensation in the presence of sodium hydride; or 2) condensation using Vorbrüggen's methods. The 5-aza- 7-deazaguanine nucleoside analogues obtained were evaluated in cell culture experiments for the inhibition of the replication of a number of RNA viruses, including BVDV, YFV, and WNV.

Antiviral Agents↗
PubMed2001

Alpha-homo-DNA and RNA form a parallel oriented non-A, non-B-type double helical structure.

Cross-talking between nucleic acids is a prerequisite for information transfer. The absence of observed base pairing interactions between pyranose and furanose nucleic acids has excluded considering the former type as a (potential) direct precursor of contemporary RNA and DNA. We observed that alpha-pyranose oligonucleotides (alpha-homo-DNA) are able to hybridize with RNA and that both nucleic acid strands are parallel oriented. Hybrids between alpha-homo-DNA and DNA are less stable. During the synthesis of alpha-homo-DNA we observed extensive conversion of N6-benzoyl-5-methylcytosine into thymine under the usual deprotection conditions of oligonucleotide synthesis. Alpha-homo-DNA:RNA represents the first hybridization system between pyranose and furanose nucleic acids. The duplex formed between alpha-homo-DNA and RNA was investigated using CD, NMR spectroscopy, and molecular modeling. The general rule that orthogonal orientation of base pairs prevents hybridization is infringed. NMR experiments demonstrate that the base moieties of alpha-homo-DNA in its complex with RNA, are equatorially oriented and that the base moieties of the parallel RNA strand are pseudoaxially oriented. Modeling experiments demonstrate that the duplex formed is different from the classical A- or B-type double stranded DNA. We observed 15 base pairs in a full helical turn. The average interphosphate distance in the RNA strand is 6.2 A and in the alpha-homo-DNA strand is 6.9 A. The interstrand P-P distance is much larger than found in the typical A- and B-DNA. Most helical parameters are different from those of natural duplexes.

Circular Dichroism↗
PubMed2001

The C(8)-(2'-deoxy-beta-D-ribofuranoside) of 7-deazaguanine: synthesis and base pairing of oligonucleotides with unusually linked nucleobases.

The 7-deazaguanine (2-aminopyrrolo[2,3-d]pyrimidin-4-one) C(8)-(2'-deoxy-beta-D-ribofuranoside) (6b), which possesses an unusual glycosylation site, was synthesized and incorporated in oligonucleotides. The oligonucleotides were prepared by solid-phase synthesis using phosphoramidite chemistry and were hybridized to form duplex DNA. Compound 6b is able to form base pairs with 2'-deoxy-5-methylisocytidine (m(5)isoC(d)) in oligonucleotide duplexes with antiparallel chain orientation and with dC in parallel duplex DNA. Thus, the C(8)-nucleoside 6b shows a similar base recognition as 2'-deoxyisoguanosine but not as 2'-deoxyguanosine. This indicates that the nucleic acid recognition not only depends on the donor-acceptor pattern of the nucleobase but is influenced by the glycosylation site. Base pairs of compound 6b formed with canonical and modified nucleosides are proposed.

Base Pairing↗
PubMed2001

Pyrazolo[3,4-d]pyrimidine nucleic acids: adjustment of dA-dT to dG-dC base pair stability.

Oligonucleotides incorporating 8-aza-7-deazapurin-2,6-diamine (pyrazolo[3,4-d]pyrimidin-4,6-diamine) nucleoside 2a or its 7-bromo derivative 2b show enhanced duplex stability compared to those containing dA. While incorporation of 2a opposite dT increases the T(m) value only slightly, the 7-bromo compound 2b forms a very stable base pair which is as strong as the dG-dC pair. Compound 2b shows a similar base discrimination in duplex DNA as dA. The base-modified nucleosides 2a,b have a significantly more stable N-glycosylic bond than the rather labile purin-2,6-diamine 2'-deoxyribonucleoside 1. Base protection with acyl groups, with which we had difficulties in the case of purine nucleoside 1, was effective with pyrazolo[3,4-d]-pyrimidine nucleosides 2a,b. Oligonucleotides containing 2a,b were obtained by solid phase synthesis employing phosphoramidite chemistry. Compound 2b harmonizes the stability of DNA duplexes. Their stability is no longer dependent on the base pair composition while they still maintain their sequence specificity. Thus, they have the potential to reduce the number of mispairs when hybridized in solution or immobilized on arrays.

Adenosine Deaminase↗
PubMed2001

The high-anti conformation of 8-aza-1,3-dideaza-2'-deoxyadenosine.

In the title compound, 4-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1H-benzotriazole, C11H14N4O3, the conformation of the N-glycosidic bond is in the high-anti range [chi = -77.1 (4) degrees ] and the 2'-deoxyribofuranose moiety adopts a 2'-endo ((2)E) sugar puckering. The 5'-hydroxyl group is disordered and has conformations ap with gamma = 171.1 (3) degrees [occupation of 61.4 (3)%] and +sc with gamma = 52.4 (6) degrees [occupation of 38.6 (3)%]. The nucleobases are stacked in the crystal state.

Adenosine↗
PubMed2001

Fluorescent DNA: the development of 7-deazapurine nucleoside triphosphates applicable for sequencing at the single molecule level.

7-Deaza-2'-deoxyadenosine and -guanosine phosphoramidite building blocks as well as corresponding 5'-triphosphate derivatives are described carrying in position 7 substituents such as iodo, hexyn-1-yl or 5-aminopentyn-1-yl residues. The phosphoramidites were used to synthesize a series of modified oligodeoxynucleotides. A systematic study of the thermal stabilities of these oligonucleotide duplexes demonstrated that the 7-substituents are well accommodated in the major groove of B-DNA. The 7-(aminoalkyn-1-yl)-7-deazapurine 2'-deoxynucleoside triphosphates were labeled with bulky fluorophores such as Rhodamine Green(R) or tetramethylrhodamine.

Biochemistry↗
PubMed2000

The N(8)-(2'-deoxyribofuranoside) of 8-aza-7-deazaadenine: a universal nucleoside forming specific hydrogen bonds with the four canonical DNA constituents.

The 8-aza-7-deazaadenine (pyrazolo[3,4-d]pyrimidin-4-amine) N(8)-(2'-deoxyribonucleoside) (2) which has an unusual glycosylation position was introduced as a universal nucleoside in oligonucleotide duplexes. These oligonucleotides were prepared by solid-phase synthesis employing phosphoramidite chemistry. Oligonucleotides incorporating the universal nucleoside 2 are capable of forming base pairs with the four normal DNA nucleosides without significant structural discrimination. The thermal stabilities of those duplexes are very similar and are only moderately reduced compared to those with regular Watson-Crick base pairs. The universal nucleoside 2 belongs to a new class of compounds that form bidentate base pairs with all four natural DNA constituents through hydrogen bonding. The base pair motifs follow the Watson-Crick or the Hoogsteen mode. Also an uncommon motif is suggested for the base pair of 2 and dG. All of the new base pairs have a different shape compared to those of the natural DNA but fit well into the DNA duplex as the distance of the anomeric carbons approximates those of the common DNA base pairs.

Adenine↗
PubMed2000

The influence of modified purine bases on the stability of parallel DNA.

The stability of the parallel-stranded (ps) DNA duplexes is increased when the dA-residues are replaced by the 7-substituted 7-deaza-2'-deoxyadenosine derivatives 3a,b or the dG-residues by the 8-aza-7-deazapurine 2'-deoxynucleosides 6 and 7a,b. Also the N-7-glycosylated adenine 5 forms stable base pairs in ps-DNA while it destabilizes oligonucleotide duplexes with antiparallel chain orientation. The presence of a 2-amino group as in compound 4b is critical for the DNA-structure, leading to a much greater destabilization of the ps-hybrids than of aps-DNA.

Base Sequence↗
PubMed2000

2-aza-2'-deoxyadenosine: synthesis, base-pairing selectivity, and stacking properties of oligonucleotides.

2-Aza-2'-deoxyadenosine (2, z2Ad) is synthesized via its 1,N6-etheno derivative 7 and enzymatically deaminated to 2-aza-2'-deoxyinosine (3). Compound 2 is converted into the phosphoramidite building block 10b. This is employed in solid-phase oligonucleotide synthesis. The 2-azapurine base forms a strong base pair with guanine, but a much weaker one with adenine, thymine, and cytosine. Oligonucleotide duplexes with dangling nucleotide residues, such as 2-aza-2'-deoxyadenosine and 7-deaza-2'-deoxyadenosine (4, c7Ad), either on one or both termini, are synthesized, and the thermal stability of the duplexes is correlated with the hydrophobic properties of the dangling nucleotide residues.

Adenosine↗
PubMed2000

2'-Deoxy-5-methylisocytidine.

In the title compound, 2-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-5-methylpyrimidin++ +-4 (1H)-one, C(10)H(15)N(3)O(4), the conformation of the N-glycosidic bond is syn and the 2-deoxyribofuranose moiety adopts an unusual (O)T(1) sugar pucker. The orientation of the exocyclic C4'-C5' bond is +sc (+gauche).

Crystallography, X-Ray↗
PubMed1998

Dissection of the roles of adenine ring nitrogen (N-1) and exocyclic amino (N-6) moieties in the interaction of 2-5A with RNase L.

To elucidate further the roles played by the adenine bases in the interaction of RNase L (EC 3.1.2.6) with the 2',5'-oligoadenylate 2-5A, p5'A2'(p5'A2')np5' A, a series of sequence-specific 1-deazaadenosine (c1A)-substituted analogues were synthesized and evaluated for their ability to bind to and activate human RNase L in comparison to earlier reported inosine-substituted congeners of 2-5A. Substitution of only the 5'-terminal adenosine of p5'A2'p5'A2 p5 A with c1A afforded an analogue with strongly diminished RNase L binding and activation ability, while replacement of the second or middle adenosine of p5 A2' p5'A2'p5' A had only a modest effect. In distinct contrast to p5'A2'p5'A2'p5'I, the c1A analogue with the third or 2'-terminal adenosine replacement approached parent p5' A2'p5'A2'p5' A in RNase L activation ability. These results permitted a further dissection of the role of various nucleotidic functional groups in the interaction of 2-5A with RNase L: specifically, that the 5'-terminal adenosine purine N-1 moiety is key for binding to RNase L, while the 2'-terminal adenosine N-6 exocyclic amino group is critical for RNase L activation.

Adenine Nucleotides↗
PubMed1998

1-Deazaadenosine: synthesis and activity of base-modified hammerhead ribozymes.

The incorporation of 1-deazaadenosine (c1A, 1b) into a hammerhead ribozyme and the resulting catalytic activity is described. For this purpose the phosphoramidite 2a and the 3'-phosphonate 2b as well as Fractosil-linked 1-deazaadenosine (3b) were prepared. The methoxyacetyl group was used for the 6-amino group protection and the triisopropylsilyl residue was introduced as the 2'-OH protecting group. Replacement of residues A14and A15.1 of the hammerhead ribozyme by 1-deazaadenosine resulted in a significantly reduced catalytic activity. Substitution of the A6, A9 and A13 residues has only a minor influence. The findings observed on ribozymes modified with 1-deazaadenosine were compared with those containing other adenosine analogues.

Base Composition↗
PubMed1998

7-Deazapurine 2'-deoxyribofuranosides are noncleavable competitive inhibitors of Escherichia coli purine nucleoside phosphorylase (PNP).

A series of 7-deazapurine 2'-deoxyribofuranosides were synthesized according to already known procedures and their substrate and inhibitor properties with purified E. coli purine nucleoside phosphorylase were examined. In agreement with previous findings, substrate activity was not detected for any of the compounds tested. Most of the nucleosides showed weak inhibition in the preliminary screening, i.e. at a concentration of about 100 microM. However some combinations of 6-chloro, 6-amino or 6-methoxy substituents with bulky hydrophobic groups at position 7 of the base and/or chloro, amino, methoxy or methylthio group at position 2 markedly enhanced affinity of such modified nucleosides for the E. coli enzyme. The most potent inhibition was observed for two nucleosides: 6-chloro- and 2-amino-6-chloro-7-deazapurine 2'-deoxyribofuranosides that show inhibition constants Ki = 2.4 and 2.3 microM, respectively. Several other compounds were also found to be good inhibitors, with inhibition constants in the range 5-50 microM. In all instances the inhibition was competitive vs. the nucleoside substrate 7-methylguanosine. Inhibition constants for 7-deazapurine nucleosides are in general several-fold lower than those observed for their purine counterparts. Therefore 7-deaza modification together with substitutions at positions 2, 6 and 7 of the base is a very promising approach to obtain competitive noncleavable inhibitors of E. coli PNP that may bind to the enzyme with inhibition constants in the microM range.

Deoxyadenosines↗
PubMed1997

Four-stranded DNA formed by isoguanine quartets: complex stoichiometry, thermal stability and resistance against exonucleases.

Single stranded DNA-fragments containing short runs of isoguanine such as d(T4iG4T4) (5) or d(iG4T4) (6) form quartet structures by self-assembly of the isoguanine residues. The stoichiometry of the complexes is deduced from mixed aggregates formed between d(T4iG4T4) and d(iG4T4). The iGd-tetrads are more stable with regard to their thermal denaturation and to their resistance against enzymatic phosphodiester hydrolysis than those formed by dG.

Base Sequence↗
PubMed1997

Parallel-stranded duplexes and quartet assemblies formed by oligonucleotides containing isoguanine.

Oligonucleotides with isoguanine-cytosine base pairs form duplexes with parallel chain orientation. This strong base pair dictates the strand polarity when additional dA-dT or N7Ad-dT pairs are present. The same is observed for the isocytosine-guanine pair. Quartet structures are built by the self-assembly of oligonucleotides containing short runs of isoguanine or 7-deazaisoguanine. New base pairs between isoguanine or guanine and 5-aza-7-deazaguanine are presented.

Base Composition↗
PubMed1996

Isoguanine quartets formed by d(T4isoG4T4): tetraplex identification and stability.

The self-aggregation of the oligonucleotide d(T4isoG4T4) (1) is investigated. Based on ion exchange HPLC experiments and CD spectroscopy, a tetrameric structure is identified. This structure was formed in the presence of sodium ions and shows almost the same chromatographic mobility on ion exchange HPLC as d(T4G4T4) (2). The ratio of aggregate versus monomer is temperature dependent and the tetraplex of [d(T4isoG4T4)]4 is more stable than that of [d(T4G4T4)]4. A mixture of d(T4isoG4T4) and d(T4G4T4) forms mixed tetraplexes containing strands of d(T4isoG4T4) and d(T4G4T4).

Chromatography, High Pressure Liquid↗
PubMed1996

Xylose-DNA: comparison of the thermodynamic stability of oligo(2'-deoxyxylonucleotide) and oligo(2'-deoxyribonucleotide) duplexes.

Measurements of differential scanning calorimetry, ultraviolet absorption and circular dichroism have been performed on two synthetic oligo(2'-deoxyxylonucleotides): (A) d[xA)3-(xT)3-(xA)3-(xT)3-T] and (B) d[(xA-xT)6-T], and on the oligo(2'-deoxyribonucleotide) (C) d[(A)3-(T)3-(A)3-(T)3]. Oligonucleotides having 2'-deoxyxylose instead of 2'-deoxyribose exhibit unusual thermodynamic, optical and structural features. At identical concentrations the transition temperatures of the oligo(2'-deoxyxylooligomers) are higher than those of the oligo(2'-deoxyribooligomers) indicating higher stability. The calorimetric transition enthalpy of (C) is 270 +/- 15 kJ . mol-1, the corresponding van't Hoff value is 280 +/- 15 kJ . (mol of cooperative unit)-1. The ratio of delta HvH/delta Hcal = 1.04 suggests all-or-none behaviour for the transition of the 2'-deoxyribose oligonucleotide. The analogous parameters of (A) are: delta Hcal = 310 +/- 30 kJ . mol-1, delta HvH = 220 +/- 30 kJ.(mol of cooperative unit)-1. The ratio of 0.71 indicates multistate melting for this compound. The sequence dependence of the thermodynamic quantities becomes apparent when the parameters of the alternating oligo(2'-deoxyxylonucleotide) d[(xA-xT)6-T] are compared to those of d[(xA)3-(xT)3-(xA)3-(xT)3-T). The values are delta Hcal = 330 +/- 30 kJ.mol-1; delta HvH = 180 +/- 15 kJ.(mol of cooperative unit)-1 delta HvH/ delta Hcal = 0.55. The transition enthalpy of the alternating oligo(2'-deoxyxylonucleotide) (B) is the highest but the cooperativity of transition is the lowest of the oligonucleotides studied. The circular dichroic spectra of the two oligo(2'-deoxyxylonucleotides) show unusual features in that d[(xA)3-(xT)3-(XA)3-(xT)3-T] exhibits a spectrum that is suggestive of a left-handed double helix, while the spectrum of the alternating oligo(2'-deoxyxylonucleotide) (B) resembles neither that of (C) nor that of (A).

Base Sequence↗