- REACTION BETWEEN NUCLEOSIDE BASE AND THE PHOSPHORYLATING AGENT DERIVED FROM 1-HYDROXYBENZOTRIAZOLE AND 2-CHLOROPHENYL PHOSPHORODICHLORIDATE
-
In the presence of 1-methylimidazole, 2-N-acyl guanine (as in 4a), thymine (as in 5a), and uracil (as in 5b) residues react readily with the phosphorylating agent derived from 2-chlorophenyl phosphorodichloridate (1a) and 1-hydroxybenzotriazole.
- Reese, Colin B.,Richards, Keith H.
-
-
Read Online
- Synthesis of isotopically labelled cardiolipins
-
A phosphotriester approach is used to access the complex phospholipid, cardiolipin (1) with polyunsaturated fatty acid chains. The synthetic method allows the specific incorporation of isotopic labels within the molecule and sets up the desired configurat
- Duralski, Andrzej A.,Spooner, Paul J.R.,Rankin, Saffron E.,Watts, Anthony
-
-
Read Online
- DINUCLEOTIDE COMPOUNDS FOR TREATING CANCERS AND MEDICAL USES THEREOF
-
The present disclosure provides the dinucleotide compounds which is useful for treating various cancers. The present disclosure also provides a composition comprising the compound or its pharmaceutically acceptable salt. The present disclosure also provides a medical use of the compound, its salt or the composition comprising the compound or its pharmaceutically acceptable salt for treating cancer. The present disclosure also provides a method of treatment of cancer comprising administering the compound, its salt or the composition comprising the compound or its salt to a subject in need of such treatment.
- -
-
Paragraph 112-113; 140
(2021/02/05)
-
- Synthetic approach to stop-codon scanning mutagenesis
-
A general combinatorial mutagenesis strategy using common dimethoxytrityl-protected mononucleotide phosphoramidites and a single orthogonally protected trinucleotide phosphoramidite (Fmoc-TAG; Fmoc = 9-fluorenylmethoxycarbonyl) was developed to scan a gene with the TAG amber stop codon with complete synthetic control. In combination with stop-codon suppressors that insert natural (e.g., alanine) or unnatural (e.g., p-benzoylphenylalanine, Bpa) amino acids, a single DNA library can be used to incorporate different amino acids for diverse purposes. Here, we scanned TAG codons through part of the gene for a model four-helix bundle protein, Rop, which regulates the copy number of ColE1 plasmids. Alanine was incorporated into Rop for mapping its binding site using an in vivo activity screen, and subtle but important differences from in vitro gel-shift studies of Rop function are evident. As a test, Bpa was incorporated using a Phe14 amber mutant isolated from the scanning library. Surprisingly, Phe14Bpa-Rop is weakly active, despite the critical role of Phe14 in Rop activity. Bpa is a photoaffinity label unnatural amino acid that can form covalent bonds with adjacent molecules upon UV irradiation. Irradiation of Phe14Bpa-Rop, which is a dimer in solution like wild-type Rop, results in covalent dimers, trimers, and tetramers. This suggests that Phe14Bpa-Rop weakly associates as a tetramer in solution and highlights the use of Bpa cross-linking as a means of trapping weak and transient interactions.
- Nie, Lihua,Lavinder, Jason J.,Sarkar, Mohosin,Stephany, Kimberly,Magliery, Thomas J.
-
experimental part
p. 6177 - 6186
(2011/06/22)
-
- Recognition and inhibition of HIV integrase by novel dinucleotides
-
HIV integrase is involved in the integration of viral DNA into chromosomal DNA, a biological process that occurs by a sequence involving HIV DNA splicing and subsequent integration steps. In the quest for small nucleotide systems with nuclease stability of the internucleotide phosphate bond and critical structural features for recognition and inhibition of HIV-1 integrase, we have discovered novel, nuclease-resistant dinucleotides with defined base sequences that are inhibitors of this key viral enzyme. Synthetic methodologies utilized for the syntheses of the novel dinucleotides include an excellent new phosphorylating agent.
- Taktakishvili, Michael,Neamati, Nouri,Pommier, Yves,Pal, Suresh,Nair, Vasu
-
p. 5671 - 5677
(2007/10/03)
-
- N6-benzyladenosine analogs of (A2′p)2A: Synthesis and activity to tobacco mosaic virus
-
Analogs of (2′-5′)oligoadenylate trimer with N6-benzyladenosine in various positions of the chain and the fully substituted trimer were synthesized by the phosphotriester method. The structures of compounds prepared were proved by UV, CD, and 1H NMR. The obtained substances inhibit replication of tobacco mosaic virus at a 10-8-10-6 M concentration, which is comparable with that of natural (A2′p)2A triadenylate.
- Kvasyuk,Kulak,Zinchenko,Barai,Mikhailopulo
-
p. 181 - 187
(2007/10/03)
-
- Synthesis and antiretroviral evaluation of new alkoxy and aryloxy phosphate derivatives of 3'-azido-3'-deoxythymidine
-
A series of new ether lipid-3'-azido-3'-deoxythymidine (AZT) conjugates (11a-g) were synthesized and evaluated for anti-HIV activity. The effect of chirality on the antiviral activity was examined through the synthesis of AZT conjugates bearing alkoxypropanols in the lipid portion of the molecule (11a-d). In addition, the long alkyl chain of alkoxyethyl ether lipid-AZT analogs was replaced with aromatic groups (11e-g), and the effect of this structural modification on activity is reported. The results of the biological tests indicate that analogs with a methyl group α to the phosphate moiety (11c,d) exhibit a marked degree of stereoselectivity with regard to their anti-HIV activity. Also, replacement of the long alkyl chain with aromatic groups in the oxyalkyl ether phospholipid-AZT conjugates leads to substantially more potent compounds (11e-g) with an anti-HIV activity comparable to that of AZT.
- Tsotinis, Andrew,Calogeropoulou, Theodora,Koufaki, Maria,Souli, Charikleia,Balzarini, Jan,De Clercq, Erik,Makriyannis, Alexandros
-
p. 3418 - 3422
(2007/10/03)
-
- Chemical synthesis and properties of an oligodeoxyribonucleotide containing a 2-deoxyribosylformamide residue
-
To elucidate the conformational properties of DNA with a 2-deoxyribosylformamide residue (dF), an oligodeoxyribonucleotide containing this abasic residue in a specific position of the nucleotide sequence was synthesized by the standard solid-phase phospho
- Shida,Iwaori,Arakawa,Sekiguchi
-
p. 961 - 964
(2007/10/02)
-
- Synthesis and biological evaluation of isomeric dinucleoside monophosphates and monomethylphosphonates of 9-β-D-arabinofuranosyladenine and related analogues
-
The 3'→5', 3'→3' and 5'→5' dinucleoside monophosphates and methylphosphonates of 9-β-D-arabinofuranosyladenine, as well as its 5'-(hydrogen phosphonate) and 5'-(methyl methylphosphonate) derivatives have been the subject of a systematic synthesis and exam
- Puech,Gosselin,Balzarini,De Clercq,Imbach
-
p. 1897 - 1907
(2007/10/02)
-
- Studies on Transfer Ribonucleic Acid and Related Compounds. XLIII. Synthesis of Oligoribonucleotides by using 5'-Selective Phosphorilation of 2'-O-Tetrahydrofuranyl Nucleosides
-
2'-O-Tetrahydrofuranyl nucleosides have been synthetized from 2,3-dihydrofuran via 3',5'-bis-tert-butyldimethylsylilnucleosides.These nucleosides were used as intermediates for oligonucleotide syntheses by the phosphotriester method.Trimers C-C-A and C-C-
- Ohtsuka, Eiko,Yamane, Akio,Ikehara, Morio
-
p. 1534 - 1543
(2007/10/02)
-
- Nucleotides, XVIII. Synthesis and Properties of (tert-Butyldimethylsilyl)guanosines, Guanosine-3'-Phosphotriesters and Guanosine-containing Oligonucleotides
-
Silylation of N2-benzoyl- (1) and N2-isobutyrylguanosin (2) by tert-butyldimethylsilyl chloride led to the various mono-, di- and tri-O-tert-butyldimethylsilyl derivatives 3-15.The synthesis of 2'- (24-31) and 3'-phosphotriesters (16
- Flockerzi, Dieter,Schlosser, Wilhelm,Pfleiderer, Wolfgang
-
p. 2069 - 2085
(2007/10/02)
-
- SYNTHESIS OF ADENYLYL-(2'->5')ADENYLYL-(2'->5')ADENOSINE
-
Three syntheses of adenylyl-(2'->5')-adenylyl-(2'->5')-adenosine (1b) are described.In the first, adenosine 2'(3') phosphate is polymerized by the action of diphenylphosphorochloridate, and the 3'->5' internucleotidic linkages and the terminal phosphoryl
- Karpeisky, Marat Yu.,Beigelman, Leon N.,Mikhailov, Sergey N.,Padyukova, Nelly Sh.,Smrt, Jiri
-
p. 156 - 166
(2007/10/02)
-
- Simplified Liquid-Phase Preparation of Four Decadeoxyribonucleotides and their Preliminary Spectroscopic Characterization
-
Four self-complementary decadeoxyribonucleotides, dApTpApTpApTpApTpApT,dApTpApTpCpGpApTpApT, dApTpApTpGpCpApTpApT and dApApApApApTpTpTpTpT, were chemically synthesized by the phosphotriester procedure.Efforts were concentrated on keeping the procedure as simple as possible, concomitant with obtaining high-purity products at each step of the process.The decamers were elaborated from the 3'-end, starting with a 3'-O-benzoylated monomer according to the scheme: monomer + monomer -> dimer + dimer -> tetramer + dimer -> hexamer + tetramer -> decamer.Putity of intermediates and of the fully blocked decamers were monitored by chromatography and by 300-MHz 1H-NMR. spectroscopy.The deblocked decadeoxyribonucleotides were characterized by their UV., CD., and 1H-NMR. spectra.
- Denny, William A.,Leupin, Werner,Kearns, David R.
-
p. 2372 - 2393
(2007/10/02)
-
- A simple approach to the syntheesis of a membrane teichoic acid fragment of Staphylococcus aureus
-
The triflate procedure of Schimdt at al. enabled us to synthesize the glycolipid, 1,2-di-O-stearoyl-3-O--sn-glycerol.Phorphsorylation of this compound with an activated and properly protected phosphatidyl derivative gave a phosphotriester derivative which, after deblocking of all protective grouops, afforded a naturally occurring teichoic acid fragment.
- Oltvoort, J. J.,Boeckel, C. A. A. van,Koning, J. H. de,Boom, J. H. van
-
-
- PHOSPHOTRIESTER APPROACH TO THE SYNTHESIS OF α-GLUCOSYLATED MONO- AND DIPHOSPHATIDYL GLYCEROLS: BACTERIAL CELL-WALL COMPONENTS
-
Two bifunctional phosphorylating agents, 2,2,2-tribromoethyl and 2-chlorophenyl phosphorodichloridate, were used with 1,2,4-triazole to assemble phosphotriester derivatives of protected α-glucosyl mono- and diphosphatidyl glycerols.Benzyl, allyl and pivaloyl groups were used for the protection of the hydroxyl functions of the glucose and glycerol moieties, respectively.The merits of the pivaloyl group are discussed.Finally, special attention is paid to the conversion of the phosphotriesters into the required phosphodiester functions.
- Boeckel, C. A. A. van,Oltvoort, J. J.,Boom, J. H. van
-
p. 3751 - 3761
(2007/10/02)
-
- Action of Toluene-p-thiol and Triethylamine on Fully Protected Thymidylyl-(3' -> 5')-thymidine. Possible Occurrence of Thiolate Ionpromoted Internucleotide Cleavage in the Synthesis of Oligonucleotides by the Phosphotriester Approach
-
When 5'-O-methoxytetrahydropyranylthymidylyl-(3' -> 5')-3'-O-methoxytetrahydropyranylthymidine o-chlorophenyl ester (12) is treated with an excess of toluene-p-thiol and triethylamine in acetonitrile solution at room temperature, it is cleaved to give 5'-O-methoxytetrahydropyranylthymidine 3'-(o-chlorophenyl) phosphate (10) and 5'-deoxy-5'-(p-tolylthio)-3'-O-methoxytetrahydropyranylthymidine (13).The bearing of this result on the synthesis of oligonucleotides by the phosphotriester approach is discussed.
- Reese, Colin B.,Titmas, Richard C.,Valente, Lydia
-
p. 2451 - 2455
(2007/10/02)
-
- Nucleotide. XIV. Substituierte β-Phenylaethyl-Gruppen. Neue Schutzgruppen fuer Oligonucleotid-Synthesen nach dem Phosphorsaeuretriester-Verfahren
-
Various o- and p-substituted β-phenylethanols (2-10) have been synthesized and investigated as blocking groups in the phosphotriester approach.A large number of 5'-O-tritylated thymidine-3'-phosphotriesters (13-36) with two different phosphate protecting groups have been prepared, characterized, and studied according to their chemical stability and usefullness for oligonucleotide syntheses.The combination of a 5'-O-monomethoxytrityl- and a 3'-(2,5-dichlorophenyl, p-nitrophenylethyl)-phosphate function as in 18 turned out to possess optimal properties as a monomeric nucleotide building block due to the fact that these blocking groups can be quantitatively and selectively be removed without harming each other by trifluoroacetic acid in chloroform to 41, by oximate to 42, and by DBU to 43.The base-catalyzed removal of the monosubstituted phenylethyl groups by DBU or DBN respectively as well as the disubstituted phenylethyl groups by triethylamine in aprotic solvents is a β-elimination process leading to phosphodiesters without attack on the P-center.
- Uhlmann, Eugen,Pfleiderer, Wolfgang
-
p. 1688 - 1703
(2007/10/02)
-
- Nucleotide. XV. Synthese und Eigenschaften von 2'-O-t-Butyldimethylsilyl-5'-O-monomethoxytritylribonucleosid-3'-phosphotriestern, Ausgangssubstanzen fuer Oligonucleotid-Synthesen
-
The syntheses of two types of fully blocked ribonucleoside 3'-phosphotriesters 6-14 have been achieved in excellent yields from 2'-O-t-butyldimethylsilyl-5'-O-monomethoxytrityl-ribonucleosides 1-5 by phosphorylation with 2-chloro- and 2,5-dichlorophenylph
- Silber, Gunter,Flockerzi, Dieter,Varma, Rajendra Singh,Charubala, Ramamurthy,Uhlmann, Eugen,Pfleiderer, Wolfgang
-
p. 1704 - 1716
(2007/10/02)
-
- 4-nitrophenyl 4-morpholinylphosphonochloridate: a convenient reagent for the synthesis of ribonucleoside mono-, di- and tri-phosphates
-
The synthesis of the crystalline and easily accessible phosphorylating agent 4-nitrophenyl 7-morpholinylphosphonochloridate is reported.Its application to the preparation of 5'-phosphorylated ribonucleosides (e.g. pA, ppA and pppA) as well as RNA fragments (e.g. pUpU and ppUpU) is demonstrated.Further, special attention is paid to the mild removal of the 4-nitrophenyl group from fully protected phosphotriester intermediates.
- Hartog, J. A. J. den,Boom, J. H. van
-
p. 285 - 290
(2007/10/02)
-
- Synthesis of the 3'-terminal decaribonucleoside nonaphosphate of yeast alanine transfer ribonucleic acid
-
The preparation, by the phosphotriester approach, of UpCpGpUpCpCpApCpCpA (23) from three protected trinucleotide blocks (19a-c) is described. The use of the o-dibromomethylbenzoyl (DBMB) protecting group in oligoribonucleotide synthesis is described for the first time. Internucleotide linkages are protected by o-chlorophenyl groups which are finally removed by treatment sith the N1, N1, N3, N3-tetramethylguanidinium salt of syn-4-nitrobenzaldoxime. The first phosphorylation step (leading to phosphodiester intermediates) is carried out by treatment with o-chlorophenyl phosphorodi-(1,2,4-triazolide) (13a; Ar = 2-C1C6H4) and then with water and triethylamine. 1-Mesitylenesulphonyl-3-nitro-1,2,4-triazole (MSNT, 14) is used as the activating agent in the second phosphorylation step.
- Jones,Rayner,Reese,Ubasawa,Ubasawa
-
p. 3075 - 3085
(2007/10/02)
-