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Methods Enzymol ; 503: 157-88, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22230569

RESUMEN

Anticalins are a novel class of small, robust proteins with designed ligand-binding properties derived from the natural lipocalin scaffold. Due to their compact molecular architecture, comprising a single polypeptide chain, they provide several benefits as protein therapeutics, such as high target specificity, good tissue penetration, low immunogenicity, tunable plasma half-life, efficient Escherichia coli expression, and suitability for furnishing with additional effector functions via genetic fusion or chemical conjugation. The lipocalins are a widespread family of proteins that naturally serve in many organisms, including humans, for the transport, storage, or sequestration of small biological compounds like vitamins and hormones. Their fold is dominated by an eight-stranded antiparallel ß-barrel, which is open to the solvent at one end. There, four loops connect the ß-strands in a pairwise manner and, altogether, they form the entry to a ligand-binding site. This loop region can be engineered via site-directed random mutagenesis in combination with genetic library selection techniques to yield "Anticalins" with exquisite specificities-and down to picomolar affinities-for prescribed molecular targets of either hapten or antigen type. Several Anticalins directed against medically relevant disease targets have been successfully engineered and can be applied, for example, for the blocking of soluble signaling factors or cell surface receptors or for tissue-specific drug targeting. While natural lipocalins were already subject to clinical studies in the past, a first Anticalin has completed Phase I trials in 2011, thus paving the way for the broad application of Anticalins as a promising novel class of biopharmaceuticals.


Asunto(s)
Proteínas de Fase Aguda/química , Proteínas Portadoras/química , Sistemas de Liberación de Medicamentos/métodos , Lipocalinas/química , Biblioteca de Péptidos , Proteínas Proto-Oncogénicas/química , Proteínas de Fase Aguda/síntesis química , Proteínas de Fase Aguda/uso terapéutico , Animales , Proteínas Portadoras/síntesis química , Proteínas Portadoras/uso terapéutico , Clonación Molecular , Ensayo de Inmunoadsorción Enzimática , Escherichia coli/química , Vectores Genéticos/química , Humanos , Lipocalina 2 , Lipocalinas/síntesis química , Lipocalinas/uso terapéutico , Mutagénesis Sitio-Dirigida/métodos , Plásmidos/química , Ingeniería de Proteínas/métodos , Proteínas Proto-Oncogénicas/síntesis química , Proteínas Proto-Oncogénicas/uso terapéutico , Proteínas Recombinantes/síntesis química , Proteínas Recombinantes/química , Proteínas Recombinantes/uso terapéutico , Especificidad por Sustrato
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