RESUMO
A series of novel 8-amino-1,3-disubstituted-imidazo[1,5-a]pyrazines was designed and synthesized as IGF-IR inhibitors.
Assuntos
Imidazóis/síntese química , Imidazóis/farmacologia , Pirazinas/síntese química , Pirazinas/farmacologia , Receptor IGF Tipo 1/antagonistas & inibidores , Trifosfato de Adenosina/metabolismo , Animais , Área Sob a Curva , Sítios de Ligação , Disponibilidade Biológica , Cristalografia por Raios X , Bases de Dados de Proteínas , Meia-Vida , Indicadores e Reagentes , Camundongos , Modelos Moleculares , Proteínas Tirosina Quinases/antagonistas & inibidores , Relação Estrutura-AtividadeRESUMO
Scaling of the exact function for the number of intramolecular nonbonded contacts in a single maximally compact linear homopolymer on hypercubic lattices is determined as a function of number N of monomers and dimension d. A representative maximally compact structure is designed and an exact recursive expression for the maximum number m(max) of contacts is derived from that design. The equivalent nonrecursive expression yields the asymptotic scaling of m(max) as (d-1)N-dN(Delta)+1, with Delta=(d-1)/d. Implications in polymer and protein studies are discussed.
RESUMO
Among the most frequent anaphylactic reactions to insects are those attributed to reduviid bugs. We report the purification and identification of the major salivary allergen of these insects. This 20-kDa protein (procalin) is a member of the lipocalin family, which includes salivary allergens from other invertebrates and mammals. An expression system capable of producing reagent quantities of recombinant allergen was developed in Saccharomyces cerevisiae. Antisera produced against recombinant protein cross-reacts with ELISA with salivary allergen. Recombinant Ag is also shown to react with sera from an allergic patient but not with control sera. By immunolocalization, the source of the salivary Ag is the salivary gland epithelium and its secretions.
Assuntos
Alérgenos/genética , Alérgenos/imunologia , Hormônios de Invertebrado/genética , Hormônios de Invertebrado/imunologia , Precursores de Proteínas/genética , Precursores de Proteínas/imunologia , Proteínas e Peptídeos Salivares/genética , Proteínas e Peptídeos Salivares/imunologia , Triatoma/genética , Triatoma/imunologia , Sequência de Aminoácidos , Anafilaxia/imunologia , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/isolamento & purificação , Expressão Gênica , Humanos , Imuno-Histoquímica , Mordeduras e Picadas de Insetos/imunologia , Proteínas de Insetos , Lipocalinas , Dados de Sequência Molecular , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Saccharomyces cerevisiae/genética , Saliva/imunologia , Glândulas Salivares/imunologiaRESUMO
Structural features of two weak inhibitors of the ZipA-FtsZ protein-protein interaction which were found to bind to overlapping but different areas of the key binding site were combined in one new series of carboxybiphenyl-indoles with improved inhibitory activity.