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1.
Nat Mater ; 15(2): 217-26, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26569474

RESUMO

The notion that animals can detect the Earth's magnetic field was once ridiculed, but is now well established. Yet the biological nature of such magnetosensing phenomenon remains unknown. Here, we report a putative magnetic receptor (Drosophila CG8198, here named MagR) and a multimeric magnetosensing rod-like protein complex, identified by theoretical postulation and genome-wide screening, and validated with cellular, biochemical, structural and biophysical methods. The magnetosensing complex consists of the identified putative magnetoreceptor and known magnetoreception-related photoreceptor cryptochromes (Cry), has the attributes of both Cry- and iron-based systems, and exhibits spontaneous alignment in magnetic fields, including that of the Earth. Such a protein complex may form the basis of magnetoreception in animals, and may lead to applications across multiple fields.


Assuntos
Proteínas Ferro-Enxofre/metabolismo , Magnetismo , Animais , Anticorpos , Materiais Biocompatíveis , Biofísica , Columbidae/metabolismo , Simulação por Computador , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Proteínas Ferro-Enxofre/genética , Microscopia Eletrônica , Modelos Moleculares , Mutagênese , Conformação Proteica , Transporte Proteico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Retina/metabolismo
2.
J Pharm Sci ; 101(10): 3896-905, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22786697

RESUMO

Using the plaque reduction assay, relatively simple bicyclic quinone molecules, as well as multiple copies thereof covalently attached to a long polyglutamate-based polymeric chain, were examined as new inhibitors of various naturally occurring strains of influenza A virus. The polymer-conjugated inhibitors were found to have a far greater potency (for some as high as two orders of magnitude when a long spacer arm was employed) than their corresponding parent molecules against the human Wuhan influenza strain. However, such polymeric inhibitors failed to exhibit higher potency compared with their small molecule predecessors against the human Puerto Rico and avian turkey influenza strains. These observations, further explored by means of molecular modeling, reveal the previously unrecognized unpredictability of the benefits of multivalency, possibly because of poor accessibility of the viral targets to polymeric agents.


Assuntos
Antivirais/química , Antivirais/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Ácido Poliglutâmico/química , Polímeros/química , Animais , Aves , Linhagem Celular , Cães , Sinergismo Farmacológico , Humanos , Influenza Aviária/tratamento farmacológico , Influenza Aviária/virologia , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Células Madin Darby de Rim Canino , Modelos Moleculares , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/virologia , Quinonas/química , Quinonas/farmacologia
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