- Synthesis of disaccharide nucleoside analogues as potential poly(ADP-ribose) polymerase-1 inhibitors
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Poly(ADP-ribose) polymerase-1 (PARP-1) is an important target in cancer therapy. We present the synthesis of novel disaccharide nucleoside analogues that resemble the central motif of poly(ADP-ribose) and test their inhibitory effects on human PARP-1. Some compounds show inhibition of enzymatic activity in vitro and thus might be interesting for further investigations.
- Zheng, Meng,Mex, Martin,G?tz, Kathrin H.,Marx, Andreas
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p. 8904 - 8907
(2018/12/10)
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- Stereoselective synthesis of 2′-modified nucleosides by using ortho-alkynyl benzoate as a gold(i)-catalyzed removable neighboring participation group
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In the present paper, we report a novel strategy for highly efficient stereoselective synthesis of 2′-modified nucleosides by using ortho-alkynyl benzoate as neighboring participation group. Subsequently, ortho-alkynyl benzoate can be removed smoothly in the presence of 5 mol% Ph3PAuCl-AgOTf in dichloromethane with H2O (1 eq.) and ethanol (6 eq.) to afford 2′-OH nucleosides in high yields and selectivity.
- Ding, Haixin,Li, Chuang,Zhou, Yirong,Hong, Sanguo,Zhang, Ning,Xiao, Qiang
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p. 1814 - 1817
(2017/01/21)
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- Poly(ADP-Ribose) - A unique natural polymer structural features, biological role and approaches to the chemical synthesis
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Poly(ADP-ribose) (PAR) is a natural polymer, taking part in numerous important cellular processes. Several enzymes are involved in biosynthesis and degradation of PAR. One of them, poly(ADP-ribose)polymerase-1 (PARP-1) is considered to be a perspective ta
- Drenichev, Mikhail S.,Mikhailov, Sergey N.
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p. 258 - 276
(2015/03/30)
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- Synthesis of Dimeric ADP-Ribose and Its Structure with Human Poly(ADP-ribose) Glycohydrolase
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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.
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p. 3558 - 3564
(2015/03/30)
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- Ribosylation of adenosine: An orthogonally protected building block for the synthesis of ADP-ribosyl oligomers
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A method to ribosylate adenosine on the 2 hydroxyl function in an α-selective fashion and in good yield is presented. Protective groups chosen for the acceptor and donor used in this glycosylation not only direct α-selectivity but also allow the construct
- Van Der Heden Van Noort, Gerbrand J.,Overkleeft, Herman S.,Van Der Marel, Gijsbert A.,Filippov, Dmitri V.
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p. 2920 - 2923
(2011/08/02)
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- Synthesis of 2′-O-α-d-ribofuranosyladenosine, monomeric unit of poly(ADP-ribose)
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The first chemical synthesis of 2′-O-α-d-ribofuranosyladenosine, monomeric unit of poly(ADP-ribose), has been achieved starting from 3′,5′-O-bis protected 9-(2-O-α-d-arabinofuranosyl-β-d-ribofuranosyl)-adenine. Configurational inversion of 2′-hydroxyl gro
- Mikhailov, Sergey N.,Kulikova, Irina V.,Nauwelaerts, Koen,Herdewijn, Piet
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p. 2871 - 2876
(2008/09/19)
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- Studies on synthesis and structure of O-β-D- ribofuranosyl(1'→2')ribonucleosides and oligonucleotides
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Minor nucleosides found in several eukaryotic initiator tRNAs(i)(Met), O-β-D-ribofuranosyl(1'→2')adenosine and -guanosine (Ar and Gr), as well as their pyrimidine analogues, were obtained from N-protected 3',5'-O-(1,1,3,3- tetraisopropyldisiloxane-1,3-diyl)ribonucleosides and 1-O-acetyl-2,3,5-tri- O-benzoyl-β-D-ribofuranose in the presence of tin tetrachloride in 1,2- dichloroethane. A crystal structure has been solved for 2'-O-ribosyluridine. The 3'-phosphoramidites of protected 2'-O-ribosylribonucleosides were prepared as the reagents for 2'-O-ribofuranosyloligonucleotides synthesis. O- β-D-Ribofuranosyl(1'→2')adenylyl(3'→5')guanosine (ArpG) was obtained and its structure was analyzed by NMR spectroscopy.
- Markiewicz, Wojciech T.,Niewczyk, Anna,Gdaniec, Zofia,Adamiak, Dorota A.,Dauter, Zbigniew,Rypniewski, Wojciech,Chmielewski, Marcin
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p. 411 - 424
(2007/10/03)
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- An efficient synthesis and physico-chemical properties of 2′-O-D-ribofuranosylnucleosides, minor tRNA components
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A high yield preparation of 9-(2-O-β-D-ribofuranosyl-β-D-ribofuranosyl)adenine, guanine- and the pyrimidine analogs (cytosine, thymine and uracil base moiety) has been achieved, and the conformational properties of the ring systems were investigated using NMR spectroscopy and X-ray.
- Mikhailov, Sergey N.,Efimtseva, Ekaterina V.,Gurskaya, Galina V.,Fomitcheva, Marina V.,Meshkov, Sergey V.,Zavodnik, Valery E.,De Bruyn, Andre,Janssen, Gerard,Rozenski, Jef,Herdewijn, Piet
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- Synthesis of Disaccharide Nucleosides and Their Incorporation into Oligonucleotides
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A high yield synthesis of 2'-O-ribofuranosyl nucleosides has been achieved and incorporation of the cytosine analogue into oligonucleotides was accomplished without difficulties.The supplementary cis diol group thus present in the middle of an oligonucleotide could be easily converted to a reactive dialdehyde moiety.
- Efimtseva, Ekaterina V.,Ermolinsky, Boris S.,Fomitcheva, Marina V.,Meshkov, Sergei V.,Padyukova, Nelly Sh.,et al.
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p. S206 - S209
(2007/10/03)
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