488-43-7Relevant articles and documents
The effect of MR1 ligand glyco-analogues on mucosal-associated invariant T (MAIT) cell activation
Braganza, Chriselle D.,Shibata, Kensuke,Fujiwara, Aisa,Motozono, Chihiro,Sonoda, Koh-Hei,Yamasaki, Sho,Stocker, Bridget L.,Timmer, Mattie S. M.
supporting information, p. 8992 - 9000 (2019/10/28)
Mucosal-associated invariant T (MAIT) cells are a subset of recently identified innate-like T lymphocytes that appear to play an important role in many pathologies ranging from viral and bacterial infection, to autoimmune disorders and cancer. MAIT cells are activated via the presentation of ligands by MR1 on antigen presenting cells to the MAIT T cell receptor (TCR), however few studies have explored the effects of systematic changes to the ligand structure on MR1 binding and MAIT cell activation. Herein, we report on the first study into the effects of changes to the sugar motif in the known MAIT cell agonists 7-hydroxy-6-methyl-8-d-ribityllumazine (RL-6-Me-7-OH) and 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU). Tetramer staining of MAIT cells revealed that the absence of the 2′-hydroxy group on the sugar backbone of lumazines improved MR1-MAIT TCR binding, which could be rationalised using computational docking studies. Although none of the lumazines activated MAIT cells, all 5-OP-RU analogues showed significant MAIT cell activation, with several analogues exhibiting comparable activity to 5-OP-RU. Docking studies with the 5-OP-RU analogues revealed different interactions between the sugar backbone and MR1 and the MAIT TCR compared to those observed for the lumazines and confirmed the importance of the 2′-hydroxy group for ligand binding and activity. Taken together, this information will assist in the development of future potent agonists and antagonists of MAIT cells.
ALCOHOL-, DIOL-, AND CARBOHYDRATE-SUBSTITUTED INDENOISOQUINOLINES AS TOPOISOMERASE I INHIBITORS
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Page/Page column 46-47, (2012/12/13)
The invention described herein pertains to substituted indenoisoquinoline compounds as described herein, wherein RA, RD, W, X and Y are defined herein, pharmaceutical compositions and formulations comprising the indenoisoquinoline compounds, their synthesis, and methods for their use in the treatment and/or prevention of cancer.
Synthesis and Hydrolytic Lability of α-Phenoxyacetamides Containing Hydroxy Groups in the N-alkyl Residue
Anelli, Pier Lucio,Brocchetta, Marino,Canipari, Sonia,Losi, Pietro,Manfredi, Giuseppe,et al.
, p. 135 - 142 (2007/10/03)
Secondary and tertiary amides of 3,5-biscarbonyl>phenoxyacetic acid bearing hydroxy groups in positions β (β-OH) and γ (γ-OH) relative to the acetamide nitrogen atom have been synthesized.Such amides easily undergo cleavage of the acetamide bond in water at neutral pH.Hydrolysis rate constant for a series of such amides and protonation constants for the corresponding leaving amines were determined.No simple correlation between the two parameters could be found.A study of the dependence of these parameters on the structural features of the substrates, such as the presence of an N-methyl group and number of β-OH and γ-OH groups, was carried out.All these features lead to enhancement of the amide hydrolysis rate and a synergistic effect is operative when both N-methyl and β-OH groups are contained in the substrate.Presence of a methyl group increases the basicity of amines whereas β-OH and γ-OH groups have the opposite effect.Mechanistic speculations seem to indicate that the abnormal lability of the acetamide bond is due to protic-like catalysis by an intramolecular OH...N hydrogen bond.
