Video Experimental Relacionado
Updated: Sep 12, 2025
09:54
Synthesis and Characterization of 1,2-Dithiolane Modified Self-Assembling Peptides
Published on: August 20, 2018
7.3K
Pegatinas peptídicas intrastrándicas que promueven el plegamiento de la hoja β, el autoensamblaje y la siembra de
Abha Dangi1, Isaac J Angera1, Juan R Del Valle1
1Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
Journal of the American Chemical Society
|August 8, 2025
Resumen
Este estudio introduce un nuevo método para estabilizar las estructuras de las hojas beta en los péptidos utilizando el grapado de la cadena lateral de cisteína. Esta técnica mejora el plegamiento de péptidos y controla el autoensamblaje de los segmentos de proteína tau, impactando la agregación.
Área de la Ciencia:
- La bioquímica
- Biología Química
- Biología estructural
Sus antecedentes:
- El grapado de la cadena lateral de los residuos de cisteína (Cys) se utiliza para limitar los péptidos, mejorando la bioactividad y la biodisponibilidad.
- Si bien es efectivo para estructuras helicoidales y de bucle, la estabilización de pliegues de láminas beta utilizando el grapado intrastrándico de Cys es menos explorada.
Objetivo del estudio:
- Investigar la eficacia del grapado i→i+2 intrastrand Cys en la estabilización de las estructuras de las hojas beta.
- Explorar la aplicación de este método en el diseño de péptidos restringidos derivados de la proteína tau y la modulación de su autoensamblaje.
Principales métodos:
- Utilizados enlazadores de E-butenilo, butinilo y m-xililo para el grapado i→i+2 Cys en péptidos modelo de horquilla beta.
- Determinar estructuras de RMN de alta resolución para analizar el impacto de las grapas en las torsiones de la columna vertebral y las interacciones entre cadenas.
- Péptidos de arco beta restringidos diseñados y sintetizados a partir de segmentos de proteína tau que incorporan macrociclado i→i+2.
Principales resultados:
- El grapado i→i+2 mejoró significativamente la población plegada de péptidos beta-hairpin.
- Las estructuras de RMN confirmaron que las grapas apoyaban las torsiones canónicas de la columna vertebral de la hoja beta y las interacciones estabilizadas entre cadenas.
- El grapado intrastrándico de un segmento de péptido tau promovió el autoensamblaje en filamentos similares a hojas beta que sembraron la agregación tau endógena.
Conclusiones:
- El grapado Di-Cys i→i+2 es un método versátil y accesible para estabilizar la estructura de la hoja beta.
- Este enfoque puede modular el autoensamblaje de péptidos amiloidogénicos competentes para las semillas, ofreciendo información sobre la agregación de proteínas.
- La técnica de grapado desarrollada proporciona una herramienta novedosa para el diseño de péptidos y el estudio de enfermedades de plegamiento erróneo de proteínas.
Videos de Conceptos Relacionados
03:03Amyloid Fibrils
9.9K
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,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.9K
01:25Protein Folding
8.6K
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...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
8.6K
01:13Protein Organization
144.0K
Overview
144.0K
02:15Protein and Protein Structure
81.3K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
A protein's shape is critical to its function. For example, an enzyme...
81.3K
02:41Protein Complex Assembly
10.9K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.9K
01:29Protein Folding Quality Check in the RER
3.8K
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...
3.8K