77244-83-8Relevant articles and documents
Targeting Mycobacterium tuberculosis Biotin Protein Ligase (MtBPL) with Nucleoside-Based Bisubstrate Adenylation Inhibitors
Bockman, Matthew R.,Kalinda, Alvin S.,Petrelli, Riccardo,De La Mora-Rey, Teresa,Tiwari, Divya,Liu, Feng,Dawadi, Surendra,Nandakumar, Madhumitha,Rhee, Kyu Y.,Schnappinger, Dirk,Finzel, Barry C.,Aldrich, Courtney C.
, p. 7349 - 7369 (2015/10/05)
Mycobacterium tuberculosis (Mtb), responsible for both latent and symptomatic tuberculosis (TB), remains the second leading cause of mortality among infectious diseases worldwide. Mycobacterial biotin protein ligase (MtBPL) is an essential enzyme in Mtb and regulates lipid metabolism through the post-translational biotinylation of acyl coenzyme A carboxylases. We report the synthesis and evaluation of a systematic series of potent nucleoside-based inhibitors of MtBPL that contain modifications to the ribofuranosyl ring of the nucleoside. All compounds were characterized by isothermal titration calorimetry (ITC) and shown to bind potently with KDs ≤ 2 nM. Additionally, we obtained high-resolution cocrystal structures for a majority of the compounds. Despite fairly uniform biochemical potency, the whole-cell Mtb activity varied greatly with minimum inhibitory concentrations (MIC) ranging from 0.78 to >100 μM. Cellular accumulation studies showed a nearly 10-fold enhancement in accumulation of a C-2′-α analogue over the corresponding C-2′-β analogue, consistent with their differential whole-cell activity.
Semisynthesis of 3′(2′)-O-(aminoacyl)-tRNA derivatives as ribosomal substrate
Cui, Zhiyong,Zhang, Biliang
, p. 297 - 310 (2008/02/08)
An efficient synthesis of (3′-terminally) 3′(2′)-O- aminoacylated pCpA derivatives is described, which could lead to the production of (aminoacyl)-tRNAs following T4 RNA ligase mediated ligation. The tetrahydrofuranyl (thf) group was used as a permanent p
Efficient synthesis of protected 3′-deoxyadenosine and 3′-deoxyguanosine from adenosine and guanosine
Cui, Zhiyong,Zhang, Lei,Zhang, Biliang
, p. 561 - 563 (2007/10/03)
Highly efficient synthesis of protected 3′-deoxyadenosine and 3′-deoxyguanosine from adenosine and guanosine were described. The 2′,3′-diol of protected adenosine and guanosine were reacted with α-acetoxyisobutyryl bromide to yield 9-(2′-O-acetyl-3′-bromo
2',3'-O-phosphonoalkylidene derivatives of ribonucleosides: Synthesis and reactivity
Endova, Magdalena,Masojidkova, Milena,Budesinsky, Milos,Rosenberg, Ivan
, p. 11151 - 11186 (2007/10/03)
A novel type of nucleotide analogues, the 2',3'-O-(1- diethylphosphono)alkylidene derivatives of ribonucleosides was prepared by redox reaction of diethyl chlorophosphite with various nucleoside orthoesters. Some of these compounds undergo interesting rearrangements when treated with nucleophiles. The configuration of the title compounds was determined by 2D-ROESY experiments. Biological activity of partially protected nucleotide analogues is also discussed.
Novel Solid-phase Synthesis of Branched Oligoribonucleotides, including a Substrate for the RNA Debranching Enzyme
Sproat, Brian S.,Beijer, Barbro,Groetli, Morten,Ryder, Ursula,Morand, Kenneth L.,Lamond, Angus I.
, p. 419 - 432 (2007/10/02)
An effective new route for synthesizing branched oligoribionucleotides in the solid phase in the 5' to 3' direction has been developed.This required the synthesis of reversed monomers, viz. protected nucleoside 5'-phosphoramidites bearing 2'-O-Fpmp and 3'
Synthesis of 2′-end modified 2′-5′-adenylate trimers
Engels, Joachim
, p. 4339 - 4342 (2007/10/02)
Trimeric 2′,5′-linked adenylates incorporating deoxyribosides and arabinoside of adenine in the 2′-end were synthesized by the phosphotriester approach using quinoline-8-sulfonyl nitrotriazoline as an effective condensing agent.
