Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates.
Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates.
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DOI：
10.1039/c1ob05637a
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发表时间：
2011-12-21
影响因子：
3.2
通讯作者：
Nilsson KP
中科院分区：
文献类型：
--
作者：
Klingstedt T;Aslund A;Simon RA;Johansson LB;Mason JJ;Nyström S;Hammarström P;Nilsson KP
用于选择性鉴定蛋白质聚集体的分子探针对于推进我们对蛋白质聚集疾病的分子发病机制的理解是重要的。在这里，我们报告的化学设计的库的阴离子发光共轭寡噻吩（LCO），它可以用作配体检测蛋白质聚集体。某些分子要求被证明是必要的，以检测：i）在淀粉样蛋白原纤维形成之前，Aβ1-42和胰岛素的早期非嗜硫黄素蛋白组装体，ii）获得在人类阿尔茨海默病脑组织中观察到的两个主要病理标志（Aβ斑块和神经元缠结）的不同光谱特征。我们的研究结果表明，上级阴离子LCO基配体应该具有由五至七个噻吩单元和延伸共轭噻吩主链的羧基组成的主链。这样的LCO将是非常有用的研究蛋白质聚集疾病的潜在分子事件，也可以用于开发新的诊断工具，这些疾病。
Molecular probes for selective identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying protein aggregation diseases. Here we report the chemical design of a library of anionic luminescent conjugated oligothiophenes (LCOs), which can be utilized as ligands for detection of protein aggregates. Certain molecular requirements were shown to be necessary for detecting: i) early non-thioflavinophilic protein assemblies of Aβ1-42 and insulin preceding the formation of amyloid fibrils and ii) for obtaining distinct spectral signatures of the two main pathological hallmarks observed in human Alzheimer’s diease brain tissue (Aβ plaques and neurofibrillary tangles). Our findings suggest that a superior anionic LCO based ligand should have a backbone consisting of five to seven thiophene units and carboxyl groups extending the conjugated thiophene backbone. Such LCOs will be highly useful for studying the underlying molecular events of protein aggregation diseases and could also be utilized for the development of novel diagnostic tools for these diseases.
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DOI：
10.1016/j.bbapap.2010.04.001
发表时间：
2010-07
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Biancalana M;Koide S
通讯作者：
Koide S
影响因子：
3.2
作者：
Nilsson, K. Peter R.;Hammarstrom, Per;Inganas, Olle
通讯作者：
Inganas, Olle
影响因子：
2.9
作者：
Nilsson, KPR;Herland, A;Inganäs, O
通讯作者：
Inganäs, O
影响因子：
3.6
作者：
Gottlieb, HE;Kotlyar, V;Nudelman, A
通讯作者：
Nudelman, A
影响因子：
5.3
作者：
Nilsson, K. Peter R.;Joshi-Barr, Shivanjali;Sigurdson, Christina J.
通讯作者：
Sigurdson, Christina J.