63 research outputs found
Solid-Phase Synthesis Of Oligonucleotides Containing 3'-Thiothymidine
No full textA 5'-O-monomethoxytritylthymidine-3'-S-thiophosphoramidite (3) has been used to prepare oligodeoxynucleotides containing 3'-thiothymidine on a solid phase support. The intermediate thiophosphites are most efficiently oxidised using tetrabutylammonium periodate
Synthesis and anticancer activity of selenium-substituted dinucleoside tetraphosphate analogues
No full textColorectal cancers (CRCs) which have elevated expression of the nucleotide pool cleanser dUTPase have been found to have increased resistance to thymidylate synthase (TS) inhibitors such as 5-fluorouracil (5-FU) and this enzyme is therefore an attractive target for potentiating anticancer activity of chemotherapy.[1] dUTPase catalyses the hydrolytic cleavage of the anhydride bond between the - and -phosphoryl moieties and following the demonstration of rAp4dU as a substrate of dUTPase,[2] we prepared a novel, selenium-substituted symmetric 5,5-dinucleoside tetraphosphate P4-SedU2 (1 Figure 1 A) using mechanochemistry. Figure 1. A Structure of selenium-substituted dinucleoside tetraphosphate substrate of dUTPase. B Tumour volume plot of mice treated with: untreated (); 1 - 1.5 mg/kg ( RALA/1 - 1.5 mg/kg (). ); 2:1 Remarkably treatment of HCT116 CRC xenografted BALB/c SCID mice with 1 formulated with the amphipathic peptide RALA (H-WEARLARALARALARHLARALARALRACEA-OH) Male mice showed significant activity in controlling cancer growth. [3] References: [1] Vértessy, B. G.; Tóth, J., Acc. Chem. Res 2009, 42, 97-106. [2] Ji, D. B., Beharry, A. A., Ford, J. M., Kool, E. T., J. Am. Chem. Soc. 2016, 138, 9005-9008. [3] Wilson, J. J., Bennie, L., Eguaogie, O., Elkashif, A., Conlon, P. F., Jena, L., McErlean, E., Buckley, N.; Englert, K.; Dunne, N. J.; Tucker, J. H. R.; Vyle, J. S.; McCarthy, H. O., JCR 2024, 369, 63-7
SYNTHESIS AND PROPERTIES OF DITHYMIDINE PHOSPHATE ANALOGS CONTAINING 3'-THIOTHYMIDINE
No full textDithymidine-3'-S-phosphorothioate (d(TspT)) has been prepared from a 5'-O-monomethoxytritylthymidine-3'-S- phosphorothioamidite (7) by activation with 5-(p- nitrophenyl)tetrazole in the presence of 3'-O- acetylthymidine. The resulting dinucleoside phosphorothioite is readily oxidised to the corresponding 3'-S-phosphorothioate using either tetrabutylammonium (TBA) perlodate or TBA oxone and has been deprotected under standard conditions to yield d(TspT). This dithymidine phosphate analogue is comparatively resistant to hydrolysis by nuclease P1, but the P-S bond is readily cleaved by aqueous solutions of either iodine or silver nitrate. Dithymidine-3'-S-phosphorodithioate (d[Tsp(s)T] was prepared in an analogous fashion using sulphur to oxidise the intermediate dinucleoside phosphoro thiolte. Absolute stereochemistry has been assigned to the diastereoisomers of d by comparing their physical and chemical properties to those of the dinucleoside phosphorothioates
New Methods For the Synthesis Of 3'-S-Phosphorothiolate Internucleoside Linkages
No full textEfficient procedures are described for the synthesis of dinucleoside phosphorothiolates using either a Michaelis-Arbusov-type reaction or a phosphotriester approach
Synthesis and Phosphorus Sulfur Bond-Cleavage Of 3'- Thiothymidylyl(3'5')Thymidine
No full textThe title compound is readily prepared from 5'-O-monomethoxytrityl-3'-thiothymidine (5); cleavage of the P–S bond can be accomplished by mild oxidative hydrolysis
Novel methodology for the preparation and purification of oligonucleotides incorporating phosphorothiolate termini
No full textA novel phosphoramidite; N,N-diisopropylamino-2-cyanoethyl-ortho-methylbenzylphosphoramidite 1, was prepared. The reaction of 1 with DMTrT and subsequent derivatisation of the phosphite triester product under solution-phase, Michaelis–Arbuzov conditions was investigated. Coupling of 1 with the terminal hydroxyl groups of support-bound oligodeoxyribonucleotides and subsequent reaction with an activated disulfide yielded oligonucleotides bearing a terminal, phosphorothiolate-linked, lipophilic moiety. The oligomers were readily purified using RP-HPLC. Silver(I)-mediated cleavage of the phosphorothiolate linkage and desalting of the oligonucleotides were performed readily in one step to yield cleanly the corresponding phosphate monester-terminated oligomers
Reversible Photocontrol of Deoxyribozyme-Catalyzed RNA Cleavage under Multiple-Turnover Conditions
No full textLights, camera, action! Photoswitchable nucleoside analogues containing o-, m-, or p-azobenzenes can be inserted in the catalytic core of RNA-cleaving 10-23 deoxyribozymes by replacing a nonconserved residue (see picture). Irradiation of the modified deoxyribozymes at 366 nm enhances RNA cleavage rates up to ninefold, thus achieving the rates observed for the unmodified deoxyribozyme
ChemInform Abstract: Nucleoside Azide—Alkyne Cycloaddition Reactions under Solvothermal Conditions or Using Copper Vials in a Ball Mill.
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