RESUMEN
A series of novel 8-amino-1,3-disubstituted-imidazo[1,5-a]pyrazines was designed and synthesized as IGF-IR inhibitors.
Asunto(s)
Imidazoles/síntesis química , Imidazoles/farmacología , Pirazinas/síntesis química , Pirazinas/farmacología , Receptor IGF Tipo 1/antagonistas & inhibidores , Adenosina Trifosfato/metabolismo , Animales , Área Bajo la Curva , Sitios de Unión , Disponibilidad Biológica , Cristalografía por Rayos X , Bases de Datos de Proteínas , Semivida , Indicadores y Reactivos , Ratones , Modelos Moleculares , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Relación Estructura-ActividadRESUMEN
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.
Asunto(s)
Proteínas Bacterianas/metabolismo , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas del Citoesqueleto/metabolismo , Diseño de Fármacos , Proteínas de Escherichia coli/metabolismo , Indoles/química , Indoles/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/química , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/química , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/química , Proteínas del Citoesqueleto/antagonistas & inhibidores , Proteínas del Citoesqueleto/química , Proteínas de Escherichia coli/antagonistas & inhibidores , Proteínas de Escherichia coli/química , Concentración 50 Inhibidora , Modelos Moleculares , Estructura Molecular , Unión Proteica/efectos de los fármacos , Estructura Terciaria de Proteína , Relación Estructura-ActividadRESUMEN
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.
Asunto(s)
Alérgenos/genética , Alérgenos/inmunología , Hormonas de Invertebrados/genética , Hormonas de Invertebrados/inmunología , Precursores de Proteínas/genética , Precursores de Proteínas/inmunología , Proteínas y Péptidos Salivales/genética , Proteínas y Péptidos Salivales/inmunología , Triatoma/genética , Triatoma/inmunología , Secuencia de Aminoácidos , Anafilaxia/inmunología , Animales , Secuencia de Bases , Clonación Molecular , ADN Complementario/genética , ADN Complementario/aislamiento & purificación , Expresión Génica , Humanos , Inmunohistoquímica , Mordeduras y Picaduras de Insectos/inmunología , Proteínas de Insectos , Lipocalinas , Datos de Secuencia Molecular , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Saccharomyces cerevisiae/genética , Saliva/inmunología , Glándulas Salivales/inmunologíaRESUMEN
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.