Alain Burger - Academia.edu (original) (raw)
Papers by Alain Burger
Journal of Physical Chemistry B, Dec 1, 2006
8-Vinyl-adenosine (8VA) is a new fluorescent nucleoside analogue with improved spectroscopic prop... more 8-Vinyl-adenosine (8VA) is a new fluorescent nucleoside analogue with improved spectroscopic properties as compared to 2-aminopurine (2AP). To further understand its photophysics, we analyzed by the timedependent density functional theory and the configuration interaction single method, the electronic properties, and transitions of 8VA in its free form and stacked with one or two flanking bases. For free 8VA, the predicted excited-state energy gaps, absorbance peak position, and oscillator strength were found to be in excellent agreement with the experimentally determined ones. Moreover, its high fluorescence quantum yield was found to be associated with the dipole-allowed S 1 f S 0 transition. Stacking of 8VA with C, T, or A in dimers or trimers resulted in fluorescence quenching through mechanisms that depend on the nature and relative orientation of the flanking base(s). When 8VA is stacked with T, quenching mainly results from nonradiative relaxation to low-lying dark excited state(s) that do not exist in free 8VA. When 8VA is stacked with A, quenching results mainly from mixing of the molecular orbitals in the ground state. Both types of quenching are thought to accompany the stacking of 8VA with C. In addition, the C-8VA-C trimer was found to exhibit a low-lying S 1 emissive state that may generate an increased fluorescence quantum yield and lifetime. The predicted photophysical properties of the trimers are highly consistent with the spectroscopic data of a series of 15-mer oligonucleotides differing only by the nature of the residues flanking the central 8VA.
Journal of Medicinal Chemistry, Jan 29, 2010
With the goal of limiting HIV-1 proliferation by increasing the mutation rate of the viral genome... more With the goal of limiting HIV-1 proliferation by increasing the mutation rate of the viral genome, we synthesized a series of pyrimidine nucleoside analogues modified in position 5 of the aglycone moiety but unmodified on the sugar part. The synthetic strategies allow us to prepare the targeted compounds directly from commercially available nucleosides. All compounds were tested for their ability to reduce HIV-1 proliferation in cell culture. Two of them (5-hydroxymethyl-2 0-dU (1c) and 5-hydroxymethyl-2 0-dC (2c)) displayed a moderate antiviral activity in single passage experiments. The same two compounds plus two additional ones (5-carbamoyl-2 0-dU (1a) and 5-carbamoylmethyl-2 0-dU (1b)) were potent inhibitors of HIV-1 RT activity in serial passage assays, in which they induced a progressive loss of HIV-1 replication. In addition, viruses collected after seven passages in the presence of 1c and 2c replicated very poorly after withdrawal of these compounds, consistent with the accumulation of deleterious mutations in the HIV-1 genome.
Nucleosides, Nucleotides & Nucleic Acids, Nov 26, 2007
Russian Journal of Bioorganic Chemistry, Nov 1, 2019
It has recently been found that derivatives of nucleotides containing а 3-hydroxychromone fluores... more It has recently been found that derivatives of nucleotides containing а 3-hydroxychromone fluorescent dye can be used as sensitive markers of conformational changes of DNA. In this work, a comparative analysis of two fluorescent nucleotide derivatives-3-hydroxychromone a (3HC) and 3HC-modified uridine (FCU)-was performed during the study of protein-nucleic acid interactions for several human DNA repair enzymes, removing damaged nucleotides: DNA glycosylases AAG, OGG1, UNG2, and MBD4 and AP endonuclease APE1. The changes of fluorescence intensity significantly depended on the nature of neighbor nucleotides and may be opposite in direction for different cases. The FCU residue located in the complementary strand opposite to damaged nucleotide or in the same strand moved by few nucleotides, is very sensitive to processes induced by DNA glycosylases in the course of formation of enzyme-substrate complexes, which include local melting and bending of the DNA chain, as well as eversion of the damaged nucleotide from DNA double helix and insertion of amino acids of the active site into the void.
Pesticide Biochemistry and Physiology, Nov 1, 1987
ABSTRACT We have recently synthesized a series of cholesterol derivatives with an acetylenic func... more ABSTRACT We have recently synthesized a series of cholesterol derivatives with an acetylenic function on the side chain at C-22 (A. Burger, C. Hetru, F. Colobert, and B. Luu, submitted for publication). These molecules were devised as potential inhibitors (suicide substrates) of the hydroxylation at C-22 which is an obligate step in the biosynthesis of ecdysone, the molting hormone of insects. We have evaluated the inhibitory activity of these molecules in an in vitro assay using prothoracic glands of larvae of Locusta, which normally synthesize large amounts of ecdysone. Two out of twelve compounds which were tested showed a marked depressory effect (up to 60% at 10−4M) which was dose dependent. This effect was irreversible. Concomitant addition of each of these inhibitors and tritiated ecdysone precursors with prothoracic glands indicate that one of these compounds selectively blocks the C-22 hydroxylase system.
PubMed, Oct 1, 1990
Prothoracic glands of the migratory locust Locusta migratoria during the postembryonnic developme... more Prothoracic glands of the migratory locust Locusta migratoria during the postembryonnic development, are the biosynthetic source of ecdysone. The production of ecdysone by these glands in vitro has been used to evaluate the inhibitory activity of four cholesteryl derivatives with an allenic function on the side chain at C-22. These molecules were devised as potential inhibitors of hydroxylation at C-22 which is an obligate step in the biosynthesis of ecdysone. Three of the four molecules tested induce a marked depressory effect of the production of ecdysone. The effect of the compound with the higher activity was dose dependent and irreversible.
PubMed, Aug 6, 2000
The antiproliferative properties of a new ribonucleoside derivative, 1-(3'-C-ethynyl-beta-D-ribof... more The antiproliferative properties of a new ribonucleoside derivative, 1-(3'-C-ethynyl-beta-D-ribofuranosyl)uracil (PJ 272) that we synthesized a few years ago, were investigated in vitro on a variety of tumor cell lines from human and murine origins and in vivo, in tumor bearing mice. Using the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we showed the ability of this compound to depress, at nanomolar concentrations, the growth of leukemia and lymphoma cultured cells. In 7 out of 8 tumor cell lines tested concentration of 50% inhibition (IC50) was found to be less than 25 nM. PJ 272 was also shown to present the same cytotoxicity against K562 Adriamycin-resistant cell line, which express a multi-drug resistance (MDR) phenotype, and its Adriamycin-sensitive parent cell line. Moreover, when injected intraperitoneally at 20 mg/kg every three days, PJ 272 was found to significantly increase the survival rate (T/C = 149%) of DBA/2 mice injected intraperitoneally with L1210 leukemic cells. Taken together, these results suggest that PJ 272 could be considered as a potentially very active drug against lymphoma and leukemia.
ChemInform, Oct 27, 2011
A Mild and Efficient Protocol for the Catalytic Silylation of Aryl Bromides.-Two different sets o... more A Mild and Efficient Protocol for the Catalytic Silylation of Aryl Bromides.-Two different sets of catalytic conditions allow the mild and efficient conversion of electron-rich and electron-deficient aryl bromides to silylarenes under unprecedented mild conditions.-(GOOSSEN, LUKAS
Dyes and Pigments, Dec 1, 2021
ChemInform, Apr 5, 2005
Antibiotics U 1200 Synthesis of New Thiazole Analogues of Pyochelin, a Siderophore of Pseudomonas... more Antibiotics U 1200 Synthesis of New Thiazole Analogues of Pyochelin, a Siderophore of Pseudomonas aeruginosa and Burkholderia cepacia. A New Conversion of Thiazolines into Thiazoles.-The new analogues (III) and (IV) of the title compound (V) are prepared in order to test their biological activity, iron chelation, and iron transport. In the course of the study a novel base-induced transformation of thiazolines into thiazoles is discovered.
Tetrahedron, Sep 1, 2003
ABSTRACT The synthesis of 5'-di- and 5'-triphosphate of 8-vinyladenosine ... more ABSTRACT The synthesis of 5'-di- and 5'-triphosphate of 8-vinyladenosine to be tested on ribonucleotide reductases requires the modification of known methods. The phosphate group was introduced by treatment with an in situ generated chlorophosphite. Protection of the 2',3' diol with acetyl groups suppressed depurination during acid removal of the phosphotriester protecting groups. The di- and triphosphate compounds were obtained by treatment of the activated adenylic acid with phosphate or pyrophosphate anions followed by removal of the acetate protecting groups. Preliminary studies were conducted on Escherichia coli ribonucleotide reductase and have shown that the diphosphate compound is efficiently reduced.
Tetrahedron, 1989
A series of allenic derivatives of cholesterol was synthesized from pregnenolone. These compounds... more A series of allenic derivatives of cholesterol was synthesized from pregnenolone. These compounds carry an allenic function at C-20 or C-22 and were devised with the aim to inhibit the C-22 hydroxylation of ecdysone biosynthesis by a suicide-substrate mechanism. The four compounds synthesized inhibit efficiently the synthesis of ecdysone in the prothoracic glands of Locusta.
Bioorganic & Medicinal Chemistry Letters, Mar 1, 2005
A novel and straightforward total synthesis of cepabactin and its iron (III) complex is described... more A novel and straightforward total synthesis of cepabactin and its iron (III) complex is described. The latter compound was compared and identified to that obtained from the cultures of Burkholderia cepacia. On treatment of the growth medium of two different strains of B. cepacia with ferric chloride, we have isolated and characterized an unexpected mixed complex of iron (III), cepabactin and pyochelin.
ChemInform, Jun 21, 1988
ChemInform Abstract The acetylenic compounds (IIa), (V) and (IX) are synthesized as shown. (IIb) ... more ChemInform Abstract The acetylenic compounds (IIa), (V) and (IX) are synthesized as shown. (IIb) are obtained via alkylation of the lithium acetylide derived from (I). All cholesteryl derivatives are prepared in order to inhibit the C-22 hydroxylation of ecdysone biosynthesis. Tests under in vitro conditions show positive effects for (IXa). A moderate activity is observed in the case of (IIa).
Tetrahedron Letters, May 1, 2004
Reaction of tributylstannyl, radical generated in situ with AIBN, with (2 0 ,5 0-di-O-tert-butyld... more Reaction of tributylstannyl, radical generated in situ with AIBN, with (2 0 ,5 0-di-O-tert-butyldimethylsilyl-3 0-C-ethynyl-b-D D-ribo-furanosyl)adenine (5) gave in 69% yield the new conformationally locked nucleosides 6 (E/Z).
Chemistry: A European Journal, Aug 19, 2018
Nucleic acids are characterized by a variety of dynamically interconverting structures that play ... more Nucleic acids are characterized by a variety of dynamically interconverting structures that play a major role in transcriptional and translational regulation as well as recombination and repair. To monitor these interconversions, FRET-based techniques can be used, but require two fluorophores that are typically large and can alter the DNA/RNA structure and protein binding. Additionally, events that do not alter the donor/acceptor distance and/or angular relationship are frequently left undetected. A more benign approach relies on fluorescent nucleobases that can substitute their native counterparts with minimal perturbation, such as the recently developed 2-thienyl-3hydroxychromone (3HCnt) and thienoguanosine (th G). To demonstrate the potency of 3HCnt and th G in deciphering interconversion mechanisms, we used the conversion of the (-)DNA copy of the HIV-1 primer binding site (-)PBS stem-loop into (+)/(-)PBS duplex, as a model system. When incorporated into the (-)PBS loop, the two probes were found to be highly sensitive to the individual steps both in the absence and the presence of a nucleic acid chaperone, providing the first complete mechanistic description of this critical process in HIV-1 replication. The combination of the two distinct probes appears to be instrumental for characterizing structural transitions of nucleic acids under various stimuli.
![Research paper thumbnail of (E)-1-Alkyl-4-[2-(alkylsulfonyl)-1-ethenyl]pyridinium Salts: Reaction with Thiol Groups Giving Rise to Chromophoric (E)-1-Alkyl-4-[2-(alkylsulfanyl)-1-ethenyl]pyridinium Salts](https://attachments.academia-assets.com/114618066/thumbnails/1.jpg)
](Chemistry: A European Journal, Jun 2, 2000
Alkyl-4-[2-(alkylsulfonyl)-1-ethenyl]pyridinium salts were synthesized in two steps. These sulfon... more Alkyl-4-[2-(alkylsulfonyl)-1-ethenyl]pyridinium salts were synthesized in two steps. These sulfones were stable at pH 7.3 and underwent a nucleophilic vinylic substitution (S N V) with mercaptans, including thiouracile, to give the corresponding 4-(thiovinyl)pyridinium salts. The X-ray diffraction structure of (E)-1-methyl-4-[2-(ethylsulfanyl)-1-ethenyl]pyridinium iodide indicated conjugation of the sulfur with the pyridinium ring. (Z)-1-Methyl-4-[2-(methylsulfanyl)-1-ethenyl]pyridinium iodide, prepared from the corresponding thioether by reaction with methyl iodide in diethyl ether, underwent isomerization to the E isomer in a first-order reaction in deuterated [D 6 ]DMSO with an activation energy of 14 kcal mol À1. At pH 7, the (E)-1-methyl-4-[2-(methylsulfonyl)-1-ethenyl]pyridinium iodide (19) reacted specifically with thiols. The reaction of this sulfone with glutathione in a TES buffer at pH 7 was a secondorder reaction (k 4100 m À1 s À1 at 30 8C) and gave the corresponding substitution product with an intense long wavelength absorption band (l max 360 nm, e 27 500 m À1 cm À1). The modification of different enzymes of known structure with 19 showed the high selectivity of this reagent towards thiol groups and its usefulness in the quantitative determination of free thiol groups in proteins.
Chemistry: A European Journal, Dec 7, 2020
In this paper, we report on the Photoinduced Electron Transfer (PET) reaction between a donor (ad... more In this paper, we report on the Photoinduced Electron Transfer (PET) reaction between a donor (adenine analog) and an acceptor (3-methoxychromone derivative) in the context of designing efficient fluorescent probes as DNA sensors. Firstly, Gibbs energy was investigated in disconnected donor-acceptor systems by Rehm-Weller equation. The oxidation potential of the adenine derivative was responsible for exergonicity of the PET reaction in separated combinations. Then, the PET reaction in donor-π-acceptor conjugates was investigated using steady-state fluorescence spectroscopy, acid-mediated PET inhibition and transient absorption techniques. In conjugated systems, PET is a favorable pathway of fluorescent quenching when an electron-rich adenine analog (d7A) was connected to the fluorophore (3MC). We found that formation of ground-state complexes even at nM concentration range dominated the dye photophysics and generated poorly emissive species likely through intermolecular PET from d7A to 3MC. On the other hand, solution acidification disrupts complexation and turns on dye emission. Bridging an electron-poor adenine analog with high oxidation potential (8d7A) to 3MC presenting low reduction potential is another alternative to prevent complex formation and produce highly emissive monomer conjugates.
Journal of Physical Chemistry B, Dec 1, 2006
8-Vinyl-adenosine (8VA) is a new fluorescent nucleoside analogue with improved spectroscopic prop... more 8-Vinyl-adenosine (8VA) is a new fluorescent nucleoside analogue with improved spectroscopic properties as compared to 2-aminopurine (2AP). To further understand its photophysics, we analyzed by the timedependent density functional theory and the configuration interaction single method, the electronic properties, and transitions of 8VA in its free form and stacked with one or two flanking bases. For free 8VA, the predicted excited-state energy gaps, absorbance peak position, and oscillator strength were found to be in excellent agreement with the experimentally determined ones. Moreover, its high fluorescence quantum yield was found to be associated with the dipole-allowed S 1 f S 0 transition. Stacking of 8VA with C, T, or A in dimers or trimers resulted in fluorescence quenching through mechanisms that depend on the nature and relative orientation of the flanking base(s). When 8VA is stacked with T, quenching mainly results from nonradiative relaxation to low-lying dark excited state(s) that do not exist in free 8VA. When 8VA is stacked with A, quenching results mainly from mixing of the molecular orbitals in the ground state. Both types of quenching are thought to accompany the stacking of 8VA with C. In addition, the C-8VA-C trimer was found to exhibit a low-lying S 1 emissive state that may generate an increased fluorescence quantum yield and lifetime. The predicted photophysical properties of the trimers are highly consistent with the spectroscopic data of a series of 15-mer oligonucleotides differing only by the nature of the residues flanking the central 8VA.
Journal of Medicinal Chemistry, Jan 29, 2010
With the goal of limiting HIV-1 proliferation by increasing the mutation rate of the viral genome... more With the goal of limiting HIV-1 proliferation by increasing the mutation rate of the viral genome, we synthesized a series of pyrimidine nucleoside analogues modified in position 5 of the aglycone moiety but unmodified on the sugar part. The synthetic strategies allow us to prepare the targeted compounds directly from commercially available nucleosides. All compounds were tested for their ability to reduce HIV-1 proliferation in cell culture. Two of them (5-hydroxymethyl-2 0-dU (1c) and 5-hydroxymethyl-2 0-dC (2c)) displayed a moderate antiviral activity in single passage experiments. The same two compounds plus two additional ones (5-carbamoyl-2 0-dU (1a) and 5-carbamoylmethyl-2 0-dU (1b)) were potent inhibitors of HIV-1 RT activity in serial passage assays, in which they induced a progressive loss of HIV-1 replication. In addition, viruses collected after seven passages in the presence of 1c and 2c replicated very poorly after withdrawal of these compounds, consistent with the accumulation of deleterious mutations in the HIV-1 genome.
Nucleosides, Nucleotides & Nucleic Acids, Nov 26, 2007
Russian Journal of Bioorganic Chemistry, Nov 1, 2019
It has recently been found that derivatives of nucleotides containing а 3-hydroxychromone fluores... more It has recently been found that derivatives of nucleotides containing а 3-hydroxychromone fluorescent dye can be used as sensitive markers of conformational changes of DNA. In this work, a comparative analysis of two fluorescent nucleotide derivatives-3-hydroxychromone a (3HC) and 3HC-modified uridine (FCU)-was performed during the study of protein-nucleic acid interactions for several human DNA repair enzymes, removing damaged nucleotides: DNA glycosylases AAG, OGG1, UNG2, and MBD4 and AP endonuclease APE1. The changes of fluorescence intensity significantly depended on the nature of neighbor nucleotides and may be opposite in direction for different cases. The FCU residue located in the complementary strand opposite to damaged nucleotide or in the same strand moved by few nucleotides, is very sensitive to processes induced by DNA glycosylases in the course of formation of enzyme-substrate complexes, which include local melting and bending of the DNA chain, as well as eversion of the damaged nucleotide from DNA double helix and insertion of amino acids of the active site into the void.
Pesticide Biochemistry and Physiology, Nov 1, 1987
ABSTRACT We have recently synthesized a series of cholesterol derivatives with an acetylenic func... more ABSTRACT We have recently synthesized a series of cholesterol derivatives with an acetylenic function on the side chain at C-22 (A. Burger, C. Hetru, F. Colobert, and B. Luu, submitted for publication). These molecules were devised as potential inhibitors (suicide substrates) of the hydroxylation at C-22 which is an obligate step in the biosynthesis of ecdysone, the molting hormone of insects. We have evaluated the inhibitory activity of these molecules in an in vitro assay using prothoracic glands of larvae of Locusta, which normally synthesize large amounts of ecdysone. Two out of twelve compounds which were tested showed a marked depressory effect (up to 60% at 10−4M) which was dose dependent. This effect was irreversible. Concomitant addition of each of these inhibitors and tritiated ecdysone precursors with prothoracic glands indicate that one of these compounds selectively blocks the C-22 hydroxylase system.
PubMed, Oct 1, 1990
Prothoracic glands of the migratory locust Locusta migratoria during the postembryonnic developme... more Prothoracic glands of the migratory locust Locusta migratoria during the postembryonnic development, are the biosynthetic source of ecdysone. The production of ecdysone by these glands in vitro has been used to evaluate the inhibitory activity of four cholesteryl derivatives with an allenic function on the side chain at C-22. These molecules were devised as potential inhibitors of hydroxylation at C-22 which is an obligate step in the biosynthesis of ecdysone. Three of the four molecules tested induce a marked depressory effect of the production of ecdysone. The effect of the compound with the higher activity was dose dependent and irreversible.
PubMed, Aug 6, 2000
The antiproliferative properties of a new ribonucleoside derivative, 1-(3'-C-ethynyl-beta-D-ribof... more The antiproliferative properties of a new ribonucleoside derivative, 1-(3'-C-ethynyl-beta-D-ribofuranosyl)uracil (PJ 272) that we synthesized a few years ago, were investigated in vitro on a variety of tumor cell lines from human and murine origins and in vivo, in tumor bearing mice. Using the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we showed the ability of this compound to depress, at nanomolar concentrations, the growth of leukemia and lymphoma cultured cells. In 7 out of 8 tumor cell lines tested concentration of 50% inhibition (IC50) was found to be less than 25 nM. PJ 272 was also shown to present the same cytotoxicity against K562 Adriamycin-resistant cell line, which express a multi-drug resistance (MDR) phenotype, and its Adriamycin-sensitive parent cell line. Moreover, when injected intraperitoneally at 20 mg/kg every three days, PJ 272 was found to significantly increase the survival rate (T/C = 149%) of DBA/2 mice injected intraperitoneally with L1210 leukemic cells. Taken together, these results suggest that PJ 272 could be considered as a potentially very active drug against lymphoma and leukemia.
ChemInform, Oct 27, 2011
A Mild and Efficient Protocol for the Catalytic Silylation of Aryl Bromides.-Two different sets o... more A Mild and Efficient Protocol for the Catalytic Silylation of Aryl Bromides.-Two different sets of catalytic conditions allow the mild and efficient conversion of electron-rich and electron-deficient aryl bromides to silylarenes under unprecedented mild conditions.-(GOOSSEN, LUKAS
Dyes and Pigments, Dec 1, 2021
ChemInform, Apr 5, 2005
Antibiotics U 1200 Synthesis of New Thiazole Analogues of Pyochelin, a Siderophore of Pseudomonas... more Antibiotics U 1200 Synthesis of New Thiazole Analogues of Pyochelin, a Siderophore of Pseudomonas aeruginosa and Burkholderia cepacia. A New Conversion of Thiazolines into Thiazoles.-The new analogues (III) and (IV) of the title compound (V) are prepared in order to test their biological activity, iron chelation, and iron transport. In the course of the study a novel base-induced transformation of thiazolines into thiazoles is discovered.
Tetrahedron, Sep 1, 2003
ABSTRACT The synthesis of 5'-di- and 5'-triphosphate of 8-vinyladenosine ... more ABSTRACT The synthesis of 5'-di- and 5'-triphosphate of 8-vinyladenosine to be tested on ribonucleotide reductases requires the modification of known methods. The phosphate group was introduced by treatment with an in situ generated chlorophosphite. Protection of the 2',3' diol with acetyl groups suppressed depurination during acid removal of the phosphotriester protecting groups. The di- and triphosphate compounds were obtained by treatment of the activated adenylic acid with phosphate or pyrophosphate anions followed by removal of the acetate protecting groups. Preliminary studies were conducted on Escherichia coli ribonucleotide reductase and have shown that the diphosphate compound is efficiently reduced.
Tetrahedron, 1989
A series of allenic derivatives of cholesterol was synthesized from pregnenolone. These compounds... more A series of allenic derivatives of cholesterol was synthesized from pregnenolone. These compounds carry an allenic function at C-20 or C-22 and were devised with the aim to inhibit the C-22 hydroxylation of ecdysone biosynthesis by a suicide-substrate mechanism. The four compounds synthesized inhibit efficiently the synthesis of ecdysone in the prothoracic glands of Locusta.
Bioorganic & Medicinal Chemistry Letters, Mar 1, 2005
A novel and straightforward total synthesis of cepabactin and its iron (III) complex is described... more A novel and straightforward total synthesis of cepabactin and its iron (III) complex is described. The latter compound was compared and identified to that obtained from the cultures of Burkholderia cepacia. On treatment of the growth medium of two different strains of B. cepacia with ferric chloride, we have isolated and characterized an unexpected mixed complex of iron (III), cepabactin and pyochelin.
ChemInform, Jun 21, 1988
ChemInform Abstract The acetylenic compounds (IIa), (V) and (IX) are synthesized as shown. (IIb) ... more ChemInform Abstract The acetylenic compounds (IIa), (V) and (IX) are synthesized as shown. (IIb) are obtained via alkylation of the lithium acetylide derived from (I). All cholesteryl derivatives are prepared in order to inhibit the C-22 hydroxylation of ecdysone biosynthesis. Tests under in vitro conditions show positive effects for (IXa). A moderate activity is observed in the case of (IIa).
Tetrahedron Letters, May 1, 2004
Reaction of tributylstannyl, radical generated in situ with AIBN, with (2 0 ,5 0-di-O-tert-butyld... more Reaction of tributylstannyl, radical generated in situ with AIBN, with (2 0 ,5 0-di-O-tert-butyldimethylsilyl-3 0-C-ethynyl-b-D D-ribo-furanosyl)adenine (5) gave in 69% yield the new conformationally locked nucleosides 6 (E/Z).
Chemistry: A European Journal, Aug 19, 2018
Nucleic acids are characterized by a variety of dynamically interconverting structures that play ... more Nucleic acids are characterized by a variety of dynamically interconverting structures that play a major role in transcriptional and translational regulation as well as recombination and repair. To monitor these interconversions, FRET-based techniques can be used, but require two fluorophores that are typically large and can alter the DNA/RNA structure and protein binding. Additionally, events that do not alter the donor/acceptor distance and/or angular relationship are frequently left undetected. A more benign approach relies on fluorescent nucleobases that can substitute their native counterparts with minimal perturbation, such as the recently developed 2-thienyl-3hydroxychromone (3HCnt) and thienoguanosine (th G). To demonstrate the potency of 3HCnt and th G in deciphering interconversion mechanisms, we used the conversion of the (-)DNA copy of the HIV-1 primer binding site (-)PBS stem-loop into (+)/(-)PBS duplex, as a model system. When incorporated into the (-)PBS loop, the two probes were found to be highly sensitive to the individual steps both in the absence and the presence of a nucleic acid chaperone, providing the first complete mechanistic description of this critical process in HIV-1 replication. The combination of the two distinct probes appears to be instrumental for characterizing structural transitions of nucleic acids under various stimuli.
Chemistry: A European Journal, Jun 2, 2000
Alkyl-4-[2-(alkylsulfonyl)-1-ethenyl]pyridinium salts were synthesized in two steps. These sulfon... more Alkyl-4-[2-(alkylsulfonyl)-1-ethenyl]pyridinium salts were synthesized in two steps. These sulfones were stable at pH 7.3 and underwent a nucleophilic vinylic substitution (S N V) with mercaptans, including thiouracile, to give the corresponding 4-(thiovinyl)pyridinium salts. The X-ray diffraction structure of (E)-1-methyl-4-[2-(ethylsulfanyl)-1-ethenyl]pyridinium iodide indicated conjugation of the sulfur with the pyridinium ring. (Z)-1-Methyl-4-[2-(methylsulfanyl)-1-ethenyl]pyridinium iodide, prepared from the corresponding thioether by reaction with methyl iodide in diethyl ether, underwent isomerization to the E isomer in a first-order reaction in deuterated [D 6 ]DMSO with an activation energy of 14 kcal mol À1. At pH 7, the (E)-1-methyl-4-[2-(methylsulfonyl)-1-ethenyl]pyridinium iodide (19) reacted specifically with thiols. The reaction of this sulfone with glutathione in a TES buffer at pH 7 was a secondorder reaction (k 4100 m À1 s À1 at 30 8C) and gave the corresponding substitution product with an intense long wavelength absorption band (l max 360 nm, e 27 500 m À1 cm À1). The modification of different enzymes of known structure with 19 showed the high selectivity of this reagent towards thiol groups and its usefulness in the quantitative determination of free thiol groups in proteins.
Chemistry: A European Journal, Dec 7, 2020
In this paper, we report on the Photoinduced Electron Transfer (PET) reaction between a donor (ad... more In this paper, we report on the Photoinduced Electron Transfer (PET) reaction between a donor (adenine analog) and an acceptor (3-methoxychromone derivative) in the context of designing efficient fluorescent probes as DNA sensors. Firstly, Gibbs energy was investigated in disconnected donor-acceptor systems by Rehm-Weller equation. The oxidation potential of the adenine derivative was responsible for exergonicity of the PET reaction in separated combinations. Then, the PET reaction in donor-π-acceptor conjugates was investigated using steady-state fluorescence spectroscopy, acid-mediated PET inhibition and transient absorption techniques. In conjugated systems, PET is a favorable pathway of fluorescent quenching when an electron-rich adenine analog (d7A) was connected to the fluorophore (3MC). We found that formation of ground-state complexes even at nM concentration range dominated the dye photophysics and generated poorly emissive species likely through intermolecular PET from d7A to 3MC. On the other hand, solution acidification disrupts complexation and turns on dye emission. Bridging an electron-poor adenine analog with high oxidation potential (8d7A) to 3MC presenting low reduction potential is another alternative to prevent complex formation and produce highly emissive monomer conjugates.