McMaster, Claire* Dotaz Zobrazit nápovědu
Simple solid-phase synthesis of 3,10-dihydro-2H-benzo[e]imidazo[1,2-b][1,2,4]thiadiazin-2-one 5,5-dioxides is described, with Fmoc-α-amino acids and 2-nitrobenzenesulfonyl chlorides (2-NosCls) being the key building blocks. Fmoc-α-amino acids were immobilized on Wang resin and transformed to the corresponding 2-nitrobenzenesulfonamides in two steps. After reduction of the nitro group, Fmoc-thioureas were synthesized followed by cyclization of the 1,2,4-benzothiadiazine-1,1-dioxide scaffold with diisopropylcarbodiimide (DIC). Cleavage of the Fmoc protecting group followed by spontaneous cyclative cleavage gave the target products in excellent crude purity.
- MeSH
- aminokyseliny chemie MeSH
- chinazoliny chemická syntéza chemie MeSH
- cyklizace MeSH
- fibrinolytika chemická syntéza chemie MeSH
- fluoreny chemie MeSH
- kyseliny sulfinové chemická syntéza chemie MeSH
- techniky kombinatorické chemie MeSH
- techniky syntézy na pevné fázi MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Solid-phase synthesis of purine derivatives bearing an α-amino acid motif in position 9 is described herein. Polymer supported amines were acylated with various Fmoc-α-amino acids and, after cleavage of the protecting group, arylation with 4,6-dichloro-5-nitropyrimidine or 2,4-dichloro-5-nitropyrimidine was performed. The second chlorine atom was replaced with various amines. Subsequent reduction of the nitro group, followed by reaction with aldehydes, afforded the purine scaffold. After cleavage from the polymer support, the target compounds were obtained in very good crude purity, good overall yields, and excellent enantiomeric purity. The anticancer activity of prepared compounds was tested in vitro against human cancer cell lines MCF7 and K562, and they were found to have mild, but clear dose-dependent effects.
Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P = 1.36 × 10-54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 × 10-19). Both risk alleles are observed at a low frequency among controls (~2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.
- MeSH
- anotace sekvence MeSH
- genetická predispozice k nemoci * MeSH
- genotypizační techniky MeSH
- HEK293 buňky MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- lidské chromozomy, pár 14 genetika MeSH
- lidské chromozomy, pár 6 genetika MeSH
- mikro RNA metabolismus MeSH
- proliferace buněk MeSH
- reportérové geny MeSH
- reprodukovatelnost výsledků MeSH
- rizikové faktory MeSH
- rodina MeSH
- sekvence nukleotidů MeSH
- typy dědičnosti genetika MeSH
- Waldenströmova makroglobulinemie genetika MeSH
- zelené fluorescenční proteiny metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH