TY - JOUR
T1 - Methylations of tryptophan-modified naphthoquinone affect its inhibitory potential toward aβ aggregation
AU - Scherzer-Attali, Roni
AU - Convertino, Marino
AU - Pellarin, Riccardo
AU - Gazit, Ehud
AU - Segal, Daniel
AU - Caflisch, Amedeo
N1 - Funding Information:
Esquema para la actualización de Ontologías de Competencias en base al Procesamiento del Lenguaje Natural y la Minería Semántica
Funding Information:
competencias en los perfiles laborales y académicos, basado en la combinación de técnicas de Procesamiento del Lenguaje Natural (PLN),Minería Semántica y Aprendizaje Ontológico, las cuales permiten crear e integrar modelos semánticos, para representar y usar las competencias. En los siguientes apartados se presenta la propuesta, que se basa en la extracción y clasificación de instancias de competencias basada en patrones, mediante técnicas de recuperación de información, tesauros y algoritmos de aprendizaje; y, finalmente, la población de ontologías de competencias con las instancias extraídas. Para ello, se propone una arquitectura que, entre otras cosas, permite la actualización de ontologías de competencias, la cual resuelve el problema de ambigüedad lingüística y semántica que se presenta en la búsqueda de competencias desde información en español.
PY - 2013/2/14
Y1 - 2013/2/14
N2 - Aggregation of amyloid beta (Aβ) is the hallmark of Alzheimer's disease (AD). Small molecules inhibiting Aβ can be valuable therapeutics for AD. We have previously reported that 1,4-naphthoquinon-2-yl-l-tryptophan (NQTrp), reduces aggregation and oligomerization of Aβ in vitro and in vivo. In silico analysis further showed that certain functional groups of NQTrp, not in the aromatic rings, are also involved in binding and inhibiting Aβ. To better understand the exact mode of action and identify the groups crucial for NQTrp inhibitory activity, we conducted structure-activity analysis. Four derivatives of NQTrp were studied in silico: a D-isomer, two single-methylated and one double-methylated derivative. In silico results showed that the NQTrp groups involved in hydrogen bonds are the anilinic NH (i.e., the NH linker between the quinone and tryptophan moieties), the quinonic carbonyls, and the carboxylic acid. These predictions were supported by in vitro results. Our results should aid in designing improved small-molecule inhibitors of Aβ aggregation for treating AD.
AB - Aggregation of amyloid beta (Aβ) is the hallmark of Alzheimer's disease (AD). Small molecules inhibiting Aβ can be valuable therapeutics for AD. We have previously reported that 1,4-naphthoquinon-2-yl-l-tryptophan (NQTrp), reduces aggregation and oligomerization of Aβ in vitro and in vivo. In silico analysis further showed that certain functional groups of NQTrp, not in the aromatic rings, are also involved in binding and inhibiting Aβ. To better understand the exact mode of action and identify the groups crucial for NQTrp inhibitory activity, we conducted structure-activity analysis. Four derivatives of NQTrp were studied in silico: a D-isomer, two single-methylated and one double-methylated derivative. In silico results showed that the NQTrp groups involved in hydrogen bonds are the anilinic NH (i.e., the NH linker between the quinone and tryptophan moieties), the quinonic carbonyls, and the carboxylic acid. These predictions were supported by in vitro results. Our results should aid in designing improved small-molecule inhibitors of Aβ aggregation for treating AD.
UR - http://www.scopus.com/inward/record.url?scp=84873894264&partnerID=8YFLogxK
U2 - 10.1021/jp309066p
DO - 10.1021/jp309066p
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AN - SCOPUS:84873894264
SN - 1520-6106
VL - 117
SP - 1780
EP - 1789
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 6
ER -