- Solventless synthesis of acyl phosphonamidates, precursors to masked bisphosphonates
-
A series of acyl phosphonamidates, the synthetic precursors to bisphosphonates, have been readily prepared from phosphoramidite type reagents and a range of acid chlorides. These reactions were performed using solventless conditions, where purification was easily achieved using column chromatography with yields ranging from 71-90%. Furthermore, we have demonstrated that these acyl phosphonamidates could be used for the preparation of unsymmetrical bisphosphonates, which do date are scarcely reported in the literature.
- Crossey, Kerri,Migaud, Marie E.
-
-
Read Online
- Synthesis of (R)-lysothiophosphatidic acid and (R)-thiophosphatidic acid
-
(R)-Thiophosphatidic acid and (R)-lysothiophosphatidic acid were obtained in an efficient synthesis from a chiral glycerol precursor via sulfurization of a bis(2-cyanoethyl) phosphite triester.
- Heeb, Norbert V.,Nambiar, Krishnan P.
-
-
Read Online
- Synthesis of Dimeric ADP-Ribose and Its Structure with Human Poly(ADP-ribose) Glycohydrolase
-
Poly(ADP-ribosyl)ation is a common post-translational modification that mediates a wide variety of cellular processes including DNA damage repair, chromatin regulation, transcription, and apoptosis. The difficulty associated with accessing poly(ADP-ribose) (PAR) in a homogeneous form has been an impediment to understanding the interactions of PAR with poly(ADP-ribose) glycohydrolase (PARG) and other binding proteins. Here we describe the chemical synthesis of the ADP-ribose dimer, and we use this compound to obtain the first human PARG substrate-enzyme cocrystal structure. Chemical synthesis of PAR is an attractive alternative to traditional enzymatic synthesis and fractionation, allowing access to products such as dimeric ADP-ribose, which has been detected but never isolated from natural sources. Additionally, we describe the synthesis of an alkynylated dimer and demonstrate that this compound can be used to synthesize PAR probes including biotin and fluorophore-labeled compounds. The fluorescently labeled ADP-ribose dimer was then utilized in a general fluorescence polarization-based PAR-protein binding assay. Finally, we use intermediates of our synthesis to access various PAR fragments, and evaluation of these compounds as substrates for PARG reveals the minimal features for substrate recognition and enzymatic cleavage. Homogeneous PAR oligomers and unnatural variants produced from chemical synthesis will allow for further detailed structural and biochemical studies on the interaction of PAR with its many protein binding partners. (Chemical Equation Presented).
- Lambrecht, Michael J.,Brichacek, Matthew,Barkauskaite, Eva,Ariza, Antonio,Ahel, Ivan,Hergenrother, Paul J.
-
supporting information
p. 3558 - 3564
(2015/03/30)
-
- Nucleoside phosphitylation using ionic liquid stabilised phosphorodiamidites and mechanochemistry
-
A range of nucleoside phosphoramidites incorporating small amino substituents have been readily synthesised using ionic liquid stabilised phosphorodiamidites coupled with mechanochemistry. The Royal Society of Chemistry.
- Crossey, Kerri,Hardacre, Christopher,Migaud, Marie E.
-
supporting information
p. 11969 - 11971
(2013/01/16)
-
- The chemical synthesis of metabolically stabilized 2-OMe-LPA analogues and preliminary studies of their inhibitory activity toward autotaxin
-
The chemical synthesis of five new metabolically stabilized 2-OMe-LPA analogues (1a-e) possessing different fatty acid residues has been performed by phosphorylation of corresponding 1-O-acyl-2-OMe-glycerols which were prepared by multistep process from racemic glycidol. The now analogues were subjected to biological characterization as autotaxin inhibitors using the FRET-based, synthetic ATX substrate FS-3. Among tested compounds 1-O-oleoyl-2-OMe-LPA (1e) appeared to be the most potent, showing ATX inhibitory activity similar to that of unmodified 1-O-oleoyl-LPA. Parallel testing showed, that similar trend was also observed for corresponding 1-O-acyl-2-OMe-phosphorothioates (2a-e, synthesized as described by us previously). 1-O-oleoyl-2-OMe-LPA (1e) was found to be resistant toward alkaline phosphatase as opposed to unmodified 1-O-oleoyl-LPA.
- Gendaszewska-Darmach, Edyta,Laska, Edyta,Rytczak, Przemys?aw,Okruszek, Andrzej
-
supporting information; experimental part
p. 2698 - 2700
(2012/05/20)
-
- Design and synthesis of biotinylated inositol 1,3,4,5-tetrakisphosphate targeting Grp1 pleckstrin homology domain
-
A bifunctional molecule containing biotin and d-myo-inositol 1,3,4,5-tetrakisphosphate was synthesized. This molecule was designed on the basis of X-ray structure of the complex of d-myo-inositol 1,3,4,5- tetrakisphosphates, Ins(1,3,4,5)P4, and
- Anraku, Kensaku,Inoue, Teruhiko,Sugimoto, Kenji,Kudo, Kota,Okamoto, Yoshinari,Morii, Takashi,Mori, Yasuo,Otsuka, Masami
-
p. 6833 - 6841
(2012/02/02)
-
- Selective synthesis of chlorophosphoramidites using ionic liquids
-
A range of chlorophosphoramidites have been prepared in ionic liquids and compared with material synthesised in molecular solvents. Through the use of ionic liquids as reaction media the moisture sensitivity and impurity issues hampering existing traditio
- Amigues, Eric J.,Hardacre, Christopher,Keane, Gillian,Migaud, Marie E.,Norman, Sarah E.,Pitner, William R.
-
scheme or table
p. 1391 - 1396
(2010/05/18)
-
- Design and synthesis of biotinylated inositol phosphates relevant to the biotin-avidin techniques
-
Six bifunctional molecules containing biotin and various inositol phosphates were synthesized. These compounds were designed on the basis of X-ray structures of the complexes of d-myo-inositol 1,4,5-triphosphates (IP 3) and phospholipase C δ pleckstrin homology domain (PLCδ PH) considering the application to the biotin-avidin techniques. The building blocks of the inositol moiety were synthesized starting with optically resolved myo-inositol derivatives and assembled to the biotin linker through a phosphate linkage. The Royal Society of Chemistry.
- Anraku, Kensaku,Inoue, Teruhiko,Sugimoto, Kenji,Morii, Takashi,Mori, Yasuo,Okamoto, Yoshinari,Otsuka, Masami
-
body text
p. 1822 - 1830
(2008/10/09)
-
- Synthesis, DNA polymerase incorporation, and enzymatic phosphate hydrolysis of formamidopyrimidine nucleoside triphosphates
-
The nucleoside triphosphates of N6-(2-deoxy-α,β-D-erythro- pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy·dGTP) and its C-nucleoside analogue (β-C-Fapy·dGTP) were synthesized. The lability of the formamide group required that nucleoside
- Imoto, Shuhei,Patro, Jennifer N.,Jiang, Yu Lin,Oka, Natsuhisa,Greenberg, Marc M.
-
p. 14606 - 14611
(2008/02/03)
-
- Drugs containing phosphoric acid derivatives as the active ingredient
-
The present invention relates to phosphoric acid derivatives represented by general formula (I), wherein each symbol is as defined in the description and nontoxic salts thereof. Because of having a TNFα production inhibitory effect, the compounds represented by general formula (I) are useful as preventives and/or remedies for rheumatoid arthritis, ulcerative colitis, Crohn's disease, hepatitis, sepsis, hemorrhagic shock, multiple sclerosis, cerebral infarction, diabetes, interstitial pneumonia, uveitis, pain, glomerulonephritis, HIV-associated diseases, cachexia, myocardial infarction, chronic heart failure, oral aphtha, Hansen's disease, infection, etc.
- -
-
-
- Solid phase synthesis
-
The present invention relates to a support system for solid phase synthesis of oligomers, such as oligonucleotides, wherein the starting compound is bound to the support via a disiloxyl linkage. Furthermore, the invention relates to a method for synthesis of oligonucleotides on a solid support. The support system comprises a stable disiloxyl linkage providing high nucleoside loadings to the support and the method allows convenient non-laborious oligomer synthesis.
- -
-
-
- Alternative procedures for the synthesis of methionine-containing peptide - oligonucleotide hybrids
-
The synthesis of methionine-containing peptide-oligonucleotide hybrids has been found to be best accomplished by a stepwise solid-phase approach in which peptide assembly using the sulfoxide derivative of methionine is followed by elongation of the oligonucleotide chain using the phosphite triester methodology, ammonia deprotection, and reduction of the sulfoxide to thioether by reaction with N-methylmercaptoacetamide. Quantitative amino acid incorporation yields could not always be achieved when the order of assembly of the two moieties was reversed, i.e. by elongating the peptide chain on a resin-linked oligonucleotide in order to avoid exposure of the thioether function to oxidizing conditions.
- Marchan, Vicente,Rodriguez-Tanty, Chryslaine,Estrada, Marta,Pedroso, Enrique,Grandas, Anna
-
p. 2495 - 2500
(2007/10/03)
-
- A Simple and Effective Chemical Phosphorylation Procedure for Biomolecules
-
A general chemical phosphorylation method based on P(III) chemistry has been developed.The system is demonstrated for the phosphorylation of oligonucleotides, directly after their synthesis on a solid support, and for the O-phosphorylation of serine, threonine, and tyrosine as well as for a serine-containing peptide.
- Bannwarth, Willi,Trzeciak, Arnold
-
p. 175 - 186
(2007/10/02)
-
- CHEMICAL 5'-PHOSPHORYLATION OF OLIGONUCLEOTIDES VALUABLE IN AUTOMATED DNA SYNTHESIS
-
A new method has been developed for the chemical 5'-phosphorylation of oligonucleotides starting from easily available phosphorous-III compounds using phosphate protecting groups which can be cleaved off via β-elimination.The hydrophobic 2-(p-nitrophenyl)
- Uhlmann, E.,Engels, J.
-
p. 1023 - 1026
(2007/10/02)
-
