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1.
Anal Chem ; 86(10): 4775-82, 2014 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-24842517

RESUMO

Lectin-functionalized silver nanoparticles have been successfully designed for use as molecular imaging agents to investigate carbohydrate-lectin interactions at the surface of mammalian cells, using surface-enhanced Raman scattering (SERS). Carbohydrate-lectin interactions are key to many cellular processes and are responsible for controlling an array of cellular interactions. In this study, lectin-functionalized silver nanoparticles were used to detect the expression of carbohydrate species at the cellular interface. The carbohydrate-lectin interactions were demonstrated using three different lectin species for three distinct cell types. Due to the known difference between the expressions of glycans in cancerous versus noncancerous cells of the same origin, this approach has been expanded to study both cancerous and noncancerous prostate cells. This has been achieved via confocal SERS mapping of the expression of the key glycan, sialic acid, on the surface of each of these cell types. In achieving such discrimination, a novel method has been created by which glycan expression can be reproducibly monitored. Comparative studies were performed using both fluorescence and SERS. SERS provided an increased discrimination over fluorescence when analyzing cell subsets to discriminate between cancerous and noncancerous cells. The success of this method means that it could be used to complement the current gold standard histopathological techniques.


Assuntos
Nanopartículas Metálicas/química , Neoplasias/metabolismo , Polissacarídeos/biossíntese , Polissacarídeos/química , Prata/química , Animais , Células CHO , Carboidratos/química , Linhagem Celular Tumoral , Cricetinae , Cricetulus , Humanos , Lectinas/química , Espalhamento de Radiação , Análise Espectral Raman
2.
Bioorg Med Chem Lett ; 17(9): 2649-55, 2007 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-17317171

RESUMO

Chronic low-dose treatment of rats with the psychomimetic drug, phencyclidine, induces regionally specific metabolic and neurochemical changes in the CNS that mirror those observed in the brains of schizophrenic patients. Recent evidence suggests that drugs targeting serotoninergic and muscarinic receptors, and in particular 5-HT(7) antagonists and M(4) agonists, exert beneficial effects in this model of schizophrenia. Compounds that display this combined pattern of activity we refer to as serominic compounds. Based upon leads from natural product screening, we have designed and synthesised such serominic compounds, which are principally arylamidine derivatives of tetrahydroisoquinolines, and shown that they have the required serominic profile in ligand binding assays and show potential antipsychotic activity in functional assays.


Assuntos
Antipsicóticos/síntese química , Antipsicóticos/farmacologia , Química Farmacêutica/métodos , Agonistas Muscarínicos/síntese química , Agonistas Muscarínicos/farmacologia , Receptor Muscarínico M4/química , Esquizofrenia/tratamento farmacológico , Anfetamina/farmacologia , Animais , Antipsicóticos/química , Atropina/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Cinética , Conformação Molecular , Agonistas Muscarínicos/química , Ratos
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