Quantitative control of Lettuce mosaic virus fitness and host defence inhibition by P1-HCPro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Structure of thrombin complexed with selective non-electrophilic inhibitors having cyclohexyl moieties at P1

The crystal structures of five new non-electrophilic β-strand-templated thrombin active-site inhibitors have been determined bound to the enzyme. Four co-crystallize with hirugen and inhibitor isomorphously to produce thrombin-hirugen crystals (monoclinic, space group C2), while one co-crystallizes in the hexagonal system, space group P65. A 1,4-substituted cyclohexyl moiety is conserved at the P1 position of all the inhibitors, along with a fused hetero-bicyclic five- and six-membered ring that occupies the P2 site. Amino, amidino and aminoimidazole groups are attached to the cyclohexyl ring for recognition at the S1 specificity site, while benzylsulfonyl and diphenyl groups enhance the binding at the S3 subsite. The cyclohexyl groups at the P1 positions of three of the inhibitors appear to be in the energetically favored chair conformation, while the imidazole-substituted cyclohexyl rings are in a boat conformation. Somewhat unexpectedly, the two cyclohexyl-aminoimidazole groups bind differently in the specificity site; the unique binding of one is heretofore unreported. The other inhibitors generally mimic arginyl binding at S1. This group of inhibitors combines the nonelectrophilicity and selectivity of DAPA-like compounds and the more optimal binding features of the S1-S3 sites of thrombin for peptidic molecules, which results in highly potent (binding constants 12 nM-16 pM, one being 1.1 μM) and selective (ranging from 140 to 20 000 times more selective compared with trypsin) inhibitors of thrombin. The binding modes of these novel inhibitors are correlated with their binding constants, as is their selectivity, in order to provide further insight for the design of therapeutic antithrombotic agents that inhibit thrombin directly at the active site.

Influência do fotoperíodo no crescimento e sobrevivência de póslarvas de piracanjuba Brycon orbignyanus (Valenciennes, 1849) (Osteichthyes, Characidae)

This paper aims at studying the influence of photoperiod on the cultivation of Brycon orbignyanus (Valenciennes, 1849) (Osteichthyes, Characidae) post-larvae submitted to four treatments: 0L-24D (L=Light; D=Dark), 10 - L14D, 14L - 10D and 24L-0D, with 3 repetitions. Post-larvae measuring 7.8±0.7mm and weighting 3.5±0.8mg were distributed in 12 aquariums (10L), stocked with 12 post-larvae per aquarium. Fishes were fed daily with Artemia sp. nanplii, in 10 days experiment. A positive relationship between the survival rate (88.9±9.7%) observed in the treatment with 24 hours of luminosity, and the lowest (58.3±8.3%), in the treatment with 24 hours of darkness. No difference was showed (P>0.05) in the mean length and weight of the post-larvae, although there was greater heterogeneity among the post-larvae cultivated at the longer darkness period.

Salmonella enteritidis in the eggs of Japanese quails (coturnix coturnix Japonica - Temminck & Schlegel, 1849) fed diets with different calcium and phosphorus levels

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Ciclo reprodutivo da tabarana, Salminus hilarii (Valenciennes, 1849) (Characidae, Salmininae) na região do baixo rio Sorocaba, SP

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A Marmota na Corte: recreação e vereda literária no cenário cultural do século XIX (1849-1852)

Pós-graduação em Letras - FCLAS

A poesia lírica na revista Guanabara (1849-1856)

Pós-graduação em Letras - FCLAS

Expressão em Escherichia coli e produção de antissoro policlonal para proteína P1 do Southern bean mosaic virus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)