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 https://doi.org/10.1002/adma.201907348 Abstract Functional amyloids produced in bacteria as nanoscale inclusion bodies are intriguing but poorly explored protein materials with wide therapeutic potential. Since they release functional polypeptides under physiological conditions, these materials can be potentially tailored as mimetic of secretory granules for slow systemic delivery of smart protein drugs. To explore this possibility, bacterial inclusion bodies formed by a self‐assembled, tumor‐targeted Pseudomonas exotoxin (PE24) are administered subcutaneously in mouse models of human metastatic colorectal cancer, for sustained secretion of tumor‐targeted therapeutic nanoparticles. These proteins are functionalized with a peptidic ligand of CXCR4, a chemokine receptor overexpressed

Abstract Five peptide ligands of four different cell surface receptors (nucleolin, CXCR1 CMKLR1 and CD44v6) have been evaluated as targeting moieties for triple-negative human breast cancers. Among them, the peptide F3, derived from phage display, promotes the fast and efficient internalization of a genetically fused GFP inside MDA-MB-231 cancer stem cells, in a specific receptor-dependent fashion. The further engineering of this protein into the modular construct F3-RK-GFP-H6 and the subsequent construct F3-RK-PE24-H6, resulted in self-assembling polypeptides that organize as discrete and regular nanoparticles. These materials, of 15-20 nm in size, show enhanced nucleolin-dependent cell penetrability. We show that the F3-RK-PE24-H6, based on the Pseudomonas aeruginosa exotoxin A (PE24)...

Un nou treball de la UAB-IBB, el l'CIBER-BBN, i l'Hospital de Sant Pau ha desenvolupat un nou biomaterial per a l'alliberament de fàrmacs continuat en el temps. Els resultats han estat publicats a Advanced Science i descriuen la creació de cossos d'inclusió artificials per a usos en biotecnologia i nanomedicina de precisió. La medicina de precisió està prenent un gran protagonisme en els nostres dies, aconseguint teràpies personalitzades més eficaçes per a cada pacient i desenvolupaments farmacològics innovadors. En el camp de l'oncologia, per exemple, s'estan desenvolupant diferents aproximacions orientades a l'alliberament dirigida i controlada dels medicaments disminuint la seva toxicitat en l'organisme. En aquest sentit, investigadors de l'CIBER de Bioenginyeria, Biomaterials i Nan

Front. Mol. Neurosci., 17 December 2019 | https://doi.org/10.3389/fnmol.2019.00306 α-Synuclein (α-Syn) forms toxic intracellular protein inclusions and transmissible amyloid structures in Parkinson’s disease (PD). Preventing α-Syn self-assembly has become one of the most promising approaches in the search for disease-modifying treatments for this neurodegenerative disorder. Here, we describe the capacity of a small molecule (ZPD-2), identified after a high-throughput screening, to inhibit α-Syn aggregation. ZPD-2 inhibits the aggregation of wild-type α-Syn and the A30P and H50Q familial variants in vitro at substoichiometric compound:protein ratios. In addition, the molecule prevents the spreading of α-Syn seeds in protein misfolding cyclic amplification assays. ZPD-2 is active against di

En un artículo publicado ayer en la revista Communications Biology, investigadores del IRTA-Instituto de Biotecnología y Biomedicina (IBB), en la Universidad Autónoma de Barcelona (UAB), y de la Universidad de Bergen y del Instituto de Investigación Marina en Noruega, presentan el descubrimiento y el origen evolutivo de una nueva subfamilia de canales de agua (acuaporinas) que puede desempeñar una función importante en la adaptación de los peces a los cambios de la salinidad ambiental. Los peces han evolucionado adaptaciones fisiológicas distintas para la vida en agua dulce o en ambientes marinos. En las especies de agua dulce el principal mecanismo fisiológico es evitar la entrada masiva de agua al organismo debido a la condición hiperosmótica de sus fluidos corporales, mientras que lo

http://engine.scichina.com/publisher/scp/journal/SCMs/doi/10.1007/s40843-019-1231-y?slug=abstract   Abstract Poly-histidine peptides such H6 (HHHHHH) are used in protein biotechnologies as purification tags, protein-assembling agents at the nanoscale and endosomal-escape entities. The pleiotropic properties of such peptides make them appealing to design protein-based smart materials or nanoparticles for imaging or drug delivery to be produced in form of recombinant proteins. However, the clinical applicability of H6-tagged proteins is restricted by the potential immunogenicity of these segments. In this study we have explored several humanized histidine-rich peptides in tumor-targeted modular proteins than bind and internalize cells through the tumoral marker CXCR4. We were particu...

https://www.sciencedirect.com/science/article/pii/S1742706119308050?via%3Dihub DOI information: 10.1016/j.actbio.2019.12.003   Abstract Fluorescent proteins are useful imaging and theranostic agents, but their potential superiority over alternative dyes is weakened by substantial photobleaching under irradiation. Enhancing protein photostability has been attempted through diverse strategies, with irregular results and limited applicability. In this context, we wondered if the controlled oligomerization of Green Fluorescent Protein (GFP) as nanoscale supramolecular complexes could stabilize the fluorophore through the newly formed protein-protein contacts, and thus, enhance its global photostability. For that, we have here analyzed the photobleaching profile of several GFP versions,

Alguns dels principals investigadors en malaltites minoritàries a Catalunya han participat en un acte al Consorci Corporació Sanitària Parc Taulí de Sabadell per donar suport a la Cursa Solidària de la UAB que donarà tot el que reculli a la investigació en aquestes malalties, a les que es dedica enguany La Marató de TV3.     El dimarts, 3 de desembre, s'ha fet un acte al Consorci Sanitari Parc Taulí de Sabadell per presentar la Cursa solidària de la UAB, en col.laboració amb l'Ajuntament de Cerdanyola del Vallès, en suport de La Marató de TV3. Joan Martí, director general del consorci hospitalari, ha obert l'acte, acompanyat de la doctora Pepi Rivera, directora clínica del Parc Taulí, i el vicerector de Relacions Institucionals i de Cultura de la UAB, Carlos Sánchez. La

El dimarts, 3 de desembre, es presentarà la Cursa Solidària UAB 2019 en suport de La Marató de TV3 -que es fa en col.laboració amb l'Ajuntament de Cerdanyola i serà el diumenge, 15 de desembre- al Consorci Corporació Sanitària Parc Taulí de Sabadell. S'hi farà una taula rodona amb investigadors de la UAB i del centre hospitalari que fan recerca en malalties minoritàries, a les que es dedica enguany la cursa. El dimarts, 3 de desembre, a les 12.30h, es farà un acte al Consorci Sanitari Parc Taulí de Sabadell per presentar la Cursa solidària de la UAB, en col.laboració amb l'Ajuntament de Cerdanyola del Vallès, en suport de La Marató de TV3. L'acte s'iniciarà amb una visita a les unitats pediàtriques amb el grup d’animació “Caulababa”. Tot seguit, a les 13.30h, el doctor Joan Martí, di

  https://onlinelibrary.wiley.com/doi/full/10.1002/advs.201902420 https://doi.org/10.1002/advs.201902420     Abstract Bacterial inclusion bodies (IBs) are mechanically stable protein particles in the microscale, which behave as robust, slow‐protein‐releasing amyloids. Upon exposure to cultured cells or upon subcutaneous or intratumor injection, these protein materials secrete functional IB polypeptides, functionally mimicking the endocrine release of peptide hormones from secretory amyloid granules. Being appealing as delivery systems for prolonged protein drug release, the development of IBs toward clinical applications is, however, severely constrained by their bacterial origin and by the undefined and protein‐to‐protein, batch‐to‐batch variable composition. In this context,