Partially and fully reconstituted complexes of the 5 S RNA and two 5 s RNA binding proteins (HL13 and HL19) from H. cutirubrum were examined using ethidium bromide binding, CD spectra, and limited nuclease digestion.The binding of 5 S RNA to HL13 was studied by means of the quenching of tryptophan fluorescence; a value of 10⁸M^-1 was estimated for the association constant in 3.7M KCl.A study of the CD spectra in the 200 to 240-nm region also indicated that this protein underwent some conformational change when bound.The addition of HL13 chased ethidium bromide bound to the 5 S RNA.The only effect observed on binding HL19 was an enhanced association constant for HL13 as inferred from a change in shape of the ethidium bromide chasing curve.Addition of HL13 also gave rise to a partial protection of the 5 S RNA against T₁ RNase digestion; in contrast, it brought about an enhanced susceptibility to pancreatic RNase digestion.Addition of HL19 had no effect in either case.Thus, protein HL13 alone is responsible for the corresponding CD and nuclease digestion observations on the native H. cutirubrum 5 S RNA-protein complex and 5 S RNA previously reported.Furthermore, despite the limited sequence homol., there is a marked structural homol., within their resp. 5 S RNA complexes, between protein HL13 from H. cutirubrum and protein EL18 from Escherichia coli.Similarly, HL19 appears to have a similar role as EL5 in the E. coli complex.

Metallomics2区 · 生物学

3-Hydroxy-4-pyridinone derivatives as metal ion and amyloid binding agents

2区 · 生物学

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作者: Chris Orvig ; Gwendolyn A. Bailey ; Jacqueline F. Cawthray ; Mariona Sodupe ; Maria A. Telpoukhovskaia ; Brent D. G. Page ; Brian O. Patrick ; Jorge Alí-Torres ; Lauren E. Scott ; Cristina Rodríguez-Rodríguez

Metal ions have been implicated in several neurodegenerative diseases, including Alzheimer's disease, as their dyshomeostasis may lead to production of reactive oxygen species as well as increased toxicity of amyloid protein aggregates. In this work, we present design and synthesis of three novel multifunctional hydroxypyridinone ligands, HL11, HL12, and HL13, bearing benzothiazole and benzoxazole functionalities. We study the ability of these compounds to bind metal ions Cu(II), Zn(II), and Fe(III), as well as their antioxidant activity and cytotoxicity. Additionally, we determine the pro-ligands' (compounds prior to chelation) propensity to target amyloid protein. Through these studies we determine the effect of combining amyloid- and metal-binding functionalities within the HPO scaffold on different aspects of AD pathology.

100 项与氯沙坦/辛伐他汀相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
高血压	临床1期	-	HANALL BIOPHARMA Co., Ltd.	-
高脂血症	临床前	-	HANALL BIOPHARMA Co., Ltd.	-

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ISC2013	N/A	缺血性卒中	-	Fluoxetine 5 mg/kg + Simvastatin 0.5 mg/kg + Ascorbic acid 20 mg/kg	鏇艱醖廠壓襯淵鹹獵襯(膚艱構選築艱鏇築觸鏇) = 獵憲醖築顧觸構願顧顧願顧選鹽顧膚觸範夢衊 (蓋鑰窪醖艱衊衊窪積願 ) 更多	-	2013-02-01
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