Video Experimental Relacionado

Updated: Sep 9, 2025

Synthesis and Characterization of 1,2-Dithiolane Modified Self-Assembling Peptides

Synthesis and Characterization of 1,2-Dithiolane Modified Self-Assembling Peptides

Published on: August 20, 2018

Síntesis química y plegamiento mediado por péptido chaperón del factor de crecimiento nervioso humano por ligadura

Nicolas Y Nötel¹, Angus E McMillan¹, Vijaya R Pattabiraman¹

¹Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland.

ACS central science

|September 2, 2025

Resumen

Los científicos sintetizaron químicamente el factor de crecimiento nervioso (NGF), una proteína para enfermedades del sistema nervioso central, superando desafíos como la hidrofobia. Este nuevo método permite diseñar variantes de NGF con mejores propiedades terapéuticas y menos efectos secundarios.

Área de la Ciencia:

Química de las proteínas
La neurociencia
Biotecnología

Sus antecedentes:

El factor de crecimiento nervioso (NGF) muestra potencial terapéutico para enfermedades del sistema nervioso central.
Su uso clínico está limitado por efectos secundarios como la hiperalgesia, derivados de amplias interacciones con los receptores.
La síntesis química de NGF es un desafío debido a su hidrofobia y la dependencia de un péptido acompañante para el plegado.

Objetivo del estudio:

Desarrollar una estrategia de síntesis química para el factor de crecimiento nervioso biológicamente activo (NGF).
Establecer una plataforma para crear variantes modificadas de NGF con perfiles terapéuticos potencialmente mejorados y efectos secundarios reducidos.
Para superar las limitaciones de la producción recombinante tradicional de proteínas complejas que requieren plegamiento asistido por chaperón.

Principales métodos:

Utilizó ligaduras de α-cetoácido-hidroxilamina (KAHA) para el ensamblaje de proteínas.
Producción recombinante empleada para el péptido chaperona N-terminal, modificado en un ácido α-ceto-terminal.
Incorpora una nueva etiqueta de solubilidad (SOLACE) y ligas KAHA formadoras de éster para ensamblar proNGF a partir de fragmentos sintéticos y recombinantes.
Se logra el plegamiento controlado y la formación de enlaces disulfuro a través del péptido acompañante, seguido de la escisión para producir un dímero activo de NGF.

Principales resultados:

Se sintetizó con éxito un dimero de factor de crecimiento nervioso (NGF) biológicamente activo utilizando un nuevo enfoque químico.
El NGF sintético demostró una actividad biológica comparable al NGF recombinante en ensayos de crecimiento de axones.
El método facilitó el plegamiento controlado y la formación de enlaces disulfuro cruciales para la estructura y la función de NGF.

Conclusiones:

Presenta una vía de síntesis química viable para el NGF, superando los obstáculos de producción anteriores.
Establece una plataforma versátil para la semisíntesis de neurotrofinas y proteínas complejas similares.
Abre vías para la ingeniería de variantes de NGF con aplicaciones terapéuticas adaptadas para trastornos neurológicos.

Más Videos Relacionados

Rapid Generation of Amyloid from Native Proteins In vitro

Rapid Generation of Amyloid from Native Proteins In vitro

Published on: December 5, 2013

Expression, Isolation, and Purification of Soluble and Insoluble Biotinylated Proteins for Nerve Tissue Regeneration

Expression, Isolation, and Purification of Soluble and Insoluble Biotinylated Proteins for Nerve Tissue Regeneration

Published on: January 22, 2014

Videos de Conceptos Relacionados

Protein Folding

Protein Folding

Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...

Molecular Chaperones and Protein Folding

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...

Bacterial Protein Maturation

Bacterial Protein Maturation

Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...

Amyloid Fibrils

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...

Protein Folding Quality Check in the RER

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...

Protein Organization

Protein Organization