Facultad de Ciencias Bioquímicas y Farmacéuticas

URI permanente para esta comunidad

https://rephip.unr.edu.ar/handle/2133/1131

Nuestra Facultad dicta las carreras de Bioquímica, Farmacia, Licenciatura en Biotecnología, Licenciatura en Química, Profesorado en Química y Licenciatura en Ciencia y Tecnología de los Alimentos. Ofrece una valiosa oferta de posgrado, con la posibilidad de cursar especializaciones, maestrías y doctorados.

Está directamente vinculada con prestigiosos centros e institutos de investigación que forman parte del Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y de la UNR, entre los que se encuentran: el Centro de Estudios Fotosintéticos y Bioquímicos (CEFOBI), el Instituto de Procesos Biotecnológicos y Químicos (IPROBYQ), el Instituto de Fisiología Experimental (IFISE), y el Instituto de Biología Molecular y Celular de Rosario (IBR), y el Instituto de Química de Rosario (IQUIR).

Contacto: Suipacha 531 S2002LRK Rosario - SF - ARGENTINA TE +54 (0) 341-4804592/3 - 4804620 - Fax +54 (0) 341-4804598.

Sitio web:http://www.fbioyf.unr.edu.ar

Consultas sobre el Repositorio:biblioteca@fbioyf.unr.edu.ar

DESCARGA LICENCIA TESIS, TESINAS, TRABAJOS FINALES: https://goo.gl/RGqbPj

DESCARGA LICENCIA OTRAS PRODUCCIONES: https://goo.gl/Tyuw6M

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Mostrando 1 - 20 de 1211

Acceso Abierto
1,3,4-oxadiazoles as inhibitors of the atypical member of the BET family bromodomain factor 3 from Trypanosoma cruzi (TcBDF3)
(Frontiers, 2024-10-01) Alonso, Victoria Lucía; Escalante, Andrea Marta; Rodríguez Araya, Elvio; Frattini, Gianfranco; Tavernelli, Luis Emilio; Moreno, Diego M.; Furlán, Ricardo Luis Eugenio; Serra, Esteban Carlos
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects millions globally, with increasing urban cases outside of Latin America. Treatment is based on two compounds, namely, benznidazole (BZ) and nifurtimox, but chronic cases pose several challenges. Targeting lysine acetylation, particularly bromodomain-containing proteins, shows promise as a novel antiparasitic target. Our research focuses on TcBDF3, a cytoplasmic protein, which is crucial for parasite differentiation that recognizes acetylated alpha-tubulin. In our previous study, A1B4 was identified as a high-affinity binder of TcBDF3, showing significant trypanocidal activity with low host toxicity in vitro. In this report, the binding of TcBDF3 to A1B4 was validated using differential scanning fluorescence, fluorescence polarization, and molecular modeling, confirming its specific interaction. Additionally, two new 1,3,4-oxadiazoles derived from A1B4 were identified, which exhibited improved trypanocide activity and cytotoxicity profiles. Furthermore, TcBDF3 was classified for the first time as an atypical divergent member of the bromodomain extraterminal family found in protists and plants. These results make TcBDF3 a unique target due to its localization and known functions not shared with higher eukaryotes, which holds promise for Chagas disease treatment.
Acceso Abierto
2-Mercaptomethyl-thiazolidines use conserved aromatic–S interactions to achieve broad-range inhibition of metallo-β-lactamases
(Royal Society of Chemistry, 2021-01-05) Rossi, María Agustina; Martínez, Verónica; Hinchliffe, Philip; Mojica, María F.; Castillo, Valerie; Moreno, Diego M.; Smith, Ryan; Spellberg, Brad; Drusano, George L.; Banchio, Claudia; Bonomo, Robert A.; Spencer, James; Vila, Alejandro J.; Mahler, Graciela; https://orcid.org/0000-0003-4720-4070; https://orcid.org/0000-0002-3697-5219; https://orcid.org/0000-0001-8611-4743; https://orcid.org/0000-0002-1380-9824; https://orcid.org/0000-0001-5493-8537; https://orcid.org/0000-0002-4602-0571; https://orcid.org/0000-0002-7978-3233; https://orcid.org/0000-0003-0612-0516
Infections caused by multidrug resistant (MDR) bacteria are a major public health threat. Carbapenems are among the most potent antimicrobial agents that are commercially available to treat MDR bacteria. Bacterial production of carbapenem-hydrolysing metallo-β-lactamases (MBLs) challenges their safety and efficacy, with subclass B1 MBLs hydrolysing almost all β-lactam antibiotics. MBL inhibitors would fulfil an urgent clinical need by prolonging the lifetime of these life-saving drugs. Here we report the synthesis and activity of a series of 2-mercaptomethyl-thiazolidines (MMTZs), designed to replicate MBL interactions with reaction intermediates or hydrolysis products. MMTZs are potent competitive inhibitors of B1 MBLs in vitro (e.g., Ki = 0.44 μM vs. NDM-1). Crystal structures of MMTZ complexes reveal similar binding patterns to the most clinically important B1 MBLs (NDM-1, VIM-2 and IMP-1), contrasting with previously studied thiol-based MBL inhibitors, such as bisthiazolidines (BTZs) or captopril stereoisomers, which exhibit lower, more variable potencies and multiple binding modes. MMTZ binding involves thiol coordination to the Zn(II) site and extensive hydrophobic interactions, burying the inhibitor more deeply within the active site than D/L-captopril. Unexpectedly, MMTZ binding features a thioether–π interaction with a conserved active-site aromatic residue, consistent with their equipotent inhibition and similar binding to multiple MBLs. MMTZs penetrate multiple Enterobacterales, inhibit NDM-1 in situ, and restore carbapenem potency against clinical isolates expressing B1 MBLs. Based on their inhibitory profile and lack of eukaryotic cell toxicity, MMTZs represent a promising scaffold for MBL inhibitor development. These results also suggest sulphur–π interactions can be exploited for general ligand design in medicinal chemistry.
Acceso Abierto
3-methylcrotonyl Coenzyme A (CoA) carboxylase complex is involved in the Xanthomonas citri subsp. citri lifestyle during citrus infection
(Public Library of Science (PLOS), 2018-06-07) Tomassetti, Mauro; Garavaglia, Betiana Soledad; Vranych, Cecilia Verónica; Gottig, Natalia; Ottado, Jorgelina; Gramajo, Hugo Cesar; Diacovich, Lautaro
Acceso Abierto
A cAMP/CRP-controlled mechanism for the incorporation of extracellular ADP-glucose in Escherichia coli involving NupC and NupG nucleoside transporters
(Nature Research, 2018-10-19) Almagro, Goizeder; Viale, Alejandro M.; Montero, Manuel; Muñoz, Francisco José; Baroja Fernández, Edurne; Mori, Hirotada; Pozueta Romero, Javier
ADP-glucose is the precursor of glycogen biosynthesis in bacteria, and a compound abundant in the starchy plant organs ingested by many mammals. Here we show that the enteric species Escherichia coli is capable of scavenging exogenous ADP-glucose for use as a glycosyl donor in glycogen biosynthesis and feed the adenine nucleotide pool. To unravel the molecular mechanisms involved in this process, we screened the E. coli single-gene deletion mutants of the Keio collection for glycogen content in ADP-glucose-containing culture medium. In comparison to wild-type (WT) cells, individual ∆nupC and ∆nupG mutants lacking the cAMP/CRP responsive inner-membrane nucleoside transporters NupC and NupG displayed reduced glycogen contents and slow ADP-glucose incorporation. In concordance, ∆cya and ∆crp mutants accumulated low levels of glycogen and slowly incorporated ADP-glucose. Two-thirds of the glycogen-excess mutants identifed during screening lacked functions that underlie envelope biogenesis and integrity, including the RpoE specifc RseA anti-sigma factor. These mutants exhibited higher ADP-glucose uptake than WT cells. The incorporation of either ∆crp, ∆nupG or ∆nupC null alleles sharply reduced the ADP-glucose incorporation and glycogen content initially witnessed in ∆rseA cells. Overall, the data showed that E. coli incorporates extracellular ADP-glucose through a cAMP/ CRP-regulated process involving the NupC and NupG nucleoside transporters that is facilitated under envelope stress conditions.
Acceso Abierto
A catalog of the highest-energy cosmic rays recorded during phase I of operation of the Pierre Auger Observatory
(American Astronomical Society, 2023-02-01) Binet, V.; Micheletti, M. I.; The Pierre Auger collaboration
Acceso Abierto
A coiled coil switch mediates cold sensing by the thermosensory protein DesK
(Wiley, 2015-10-08) Saita, Emilio Adolfo; Abriata, Luciano Andrés; Tsai, Yi-Ting; Trajtenberg, Felipe; Lemmin, Thomas; Buschiazzo, Alejandro; Dal Peraro, Matteo; De Mendoza, Diego; Albanesi, Daniela
The thermosensor histidine kinase DesK from Bacillus subtilis senses changes in membrane fluidity initiating an adaptive response. Structural changes in DesK have been implicated in transmembrane signaling, but direct evidence is still lacking. On the basis of structure-guided mutagenesis, we now propose a mechanism of DesK-mediated signal sensing and transduction. The data indicate that stabilization/destabilization of a 2-helix coiled coil, which connects the transmembrane sensory domain of DesK to its cytosolic catalytic region, is crucial to control its signaling state. Computational modeling and simulations reveal couplings between protein, water and membrane mechanics. We propose that membrane thickening is the main driving force for signal sensing and that it acts by inducing helix stretching and rotation prompting an asymmetric kinase-competent state. Overall, the known structural changes of the sensor kinase, as well as further dynamic rearrangements that we now predict, consistently link structure determinants to activity modulation.
Acceso Abierto
A combined experimental and molecular simulation study of factors influencing interaction of quinoa proteins–carrageenan
(Elsevier, 2018-02-01) Montellano Duran, Natalia; Spelzini, Darío; Wayllace, Natanel; Boeris, Valeria; Baroso da Silva, Fernando; Zepeda Rivera, Martha. Harvard University; United States: for English correction in the manuscript.; Rice University; United States: for the computing hours; University College Dublin; Ireland.
Acceso Abierto
A comparison of methods for the detection of Ascochyta rabiei in chickpea seeds
(Grupo Paulista de Fitopatologia, 2019-07-10) Sautua, Francisco José; Casey, Santiago Agustín; Zapata, Raúl Lorenzo; Scandiani, María Mercedes; Carmona, Marcelo Aníbal
Acceso Abierto
A conditional mutant of the fatty acid synthase unveils unexpected cross talks in mycobacterial lipid metabolism
(Royal Society, 2017-02-22) Cabruja, Matías Ezequiel; Mondino, Sonia Soledad; Tsai, Yi-Ting; Lara, María Julia; Gramajo, Hugo Cesar; Gago, Gabriela
Acceso Abierto
A convenient and eco-friendly cerium(III) chloride-catalysed synthesis of methoxime derivatives of aromatic aldehydes and ketones
(The Royal Society, 2018-05-23) Cortés, Iván; Kaufman, Teodoro Saúl; Bracca, Andrea Beatriz Juana
Acceso Abierto
A convenient approach to an advanced intermediate toward the naturally occurring, bioactive 6-substituted 5-hydroxy-4-aryl-1H-quinolin-2-ones
(Royal Society of Chemistry, 2016-01-26) Simonetti, Sebastián Osvaldo; Larghi, Enrique Leandro; Kaufman, Teodoro Saúl
Acceso Abierto
A critical review on the development of optical sensors for the determination of heavy metals in water samples. The case of mercury(II) ion
(American Chemical Society, 2022-11-08) Escandar, Graciela Mónica; Olivieri, Alejandro César
Acceso Abierto
A disordered region retains the full protease inhibitor activity and the capacity to induce CD8+ T cells in vivo of the oral vaccine adjuvant U-Omp19
(Elsevier, 2022-09-06) Darriba, María Laura; Pueblas Castro, Celeste; Coria, Lorena M.; Bruno, Laura; Cerutti, María Laura; Otero, Lisandro H.; Chemes, Lucía B.; Rasia, Rodolfo M.; Klinke, Sebastián; Cassataro, Juliana; Pasquevich, Karina A.
Acceso Abierto
A duo of Potassium-responsive Histidine Kinases govern the multicellular destiny of Bacillus subtilis
(American Society for Microbiology, 2015-07-07) Grau, Roberto Ricardo; De Oña, Paula; Kunert, Maritta; Leñini, Cecilia; Gallegos Monterrosa, Ramses; Mhatre, Eisha; Vileta, Darío; Donato, Verónica; Hölscher, Theresa; Boland, Sebastian; Kuipers, Oscar P.; Kovács, Ákos T.; http://orcid.org/0000-0001-6430-7122; http://orcid.org/0000-0001-6784-2534
Multicellular biofilm formation and surface motility are bacterial behaviors considered mutually exclusive. However, the basic decision to move over or stay attached to a surface is poorly understood. Here, we discover that in Bacillus subtilis, the key root biofilm-controlling transcription factor Spo0A~Pi (phosphorylated Spo0A) governs the flagellum-independent mechanism of social sliding motility. A Spo0A-deficient strain was totally unable to slide and colonize plant roots, evidencing the important role that sliding might play in natural settings. Microarray experiments plus subsequent genetic characterization showed that the machineries of sliding and biofilm formation share the same main components (i.e., surfactin, the hydrophobin BslA, exopolysaccharide, and de novo-formed fatty acids). Sliding proficiency was transduced by the Spo0A-phosphorelay histidine kinases KinB and KinC. We discovered that potassium, a previously known inhibitor of KinC-dependent biofilm formation, is the specific sliding-activating signal through a thus-far-unnoticed cytosolic domain of KinB, which resembles the selectivity filter sequence of potassium channels. The differential expression of the Spo0A~Pireporter abrB gene and the different levels of the constitutively active form of Spo0A, Sad67, in spo0A cells grown in optimized media that simultaneously stimulate motile and sessile behaviors uncover the spatiotemporal response of KinB and KinC to potassium and the gradual increase in Spo0A~Pi that orchestrates the sequential activation of sliding, followed by sessile biofilm formation and finally sporulation in the same population. Overall, these results provide insights into how multicellular behaviors formerly believed to be antagonistic are coordinately activated in benefit of the bacterium and its interaction with the host. IMPORTANCE Alternation between motile and sessile behaviors is central to bacterial adaptation, survival, and colonization. However, how is the collective decision to move over or stay attached to a surface controlled? Here, we use the model plantbeneficial bacterium Bacillus subtilis to answer this question. Remarkably, we discover that sessile biofilm formation and social sliding motility share the same structural components and the Spo0A regulatory network via sensor kinases, KinB and KinC. Potassium, an inhibitor of KinC-dependent biofilm formation, triggers sliding via a potassium-perceiving cytosolic domain of KinB that resembles the selectivity filter of potassium channels. The spatiotemporal response of these kinases to variable potassium levels and the gradual increase in Spo0A~Pi levels that orchestrates the activation of sliding before biofilm formation shed light on how multicellular behaviors formerly believed to be antagonistic work together to benefit the population fitness.
Acceso Abierto
A general reaction mechanism for carbapenem hydrolysis by mononuclear and binuclear metallo-β-lactamases
(Nature, 2017-09-14) Lisa, María Natalia; Palacios, Antonela R.; Aitha, Mahesh; González, Mariano M.; Moreno, Diego M.; Crowder, Michael W.; Bonomo, Robert A.; Spencer, James; Tierney, David L.; Llarrull, Leticia Irene; Vila, Alejandro J.
Acceso Abierto
A genetic screen for mutations affecting temperature sensing in Bacillus subtilis
(Microbiology Society, 2018-11-15) Díaz, Alejandra Raquel; Porrini, Lucía; De Mendoza, Diego; Mansilla, María Cecilia
Two component systems, composed of a receptor histidine kinase and a cytoplasmic response regulator, regulate pivotal cellular processes in microorganisms. Here we describe a new screening procedure for the identification of amino acids that are crucial for the functioning of DesK, a prototypic thermosensor histidine kinase from Bacillus subtilis. This experimental strategy involves random mutagenesis of the membrane sensor domain of the DesK coding sequence, followed by the use of a detection procedure based on changes in the colony morphogenesis that take place during the sporulation programme of B. subtilis. This method permitted us the recovery of mutants defective in DesK temperature sensing. This screening approach could be applied to all histidine kinases of B. subtilis and also to kinases of other bacteria that are functionally expressed in this organism. Moreover, this reporter assay could be expanded to develop reporter assays for a variety of transcriptionally regulated systems.
Acceso Abierto
A green method for the quantification of plastics-derived endocrine disruptors in beverages by chemometrics-assisted liquid chromatography with simultaneous diode array and fluorescent detection
(Elsevier, 2016-10) Pellegrino Vidal, Rocío Belén; Ibañez, Gabriela Alejandra; Escandar, Graciela Mónica
Acceso Abierto
A green-analytical chemistry method for agrochemical-residue analysis in vegetables
(Elsevier, 2016-09) Carabajal, Maira Daniela; Arancibia, Juan Alberto; Escandar, Graciela Mónica
Acceso Abierto
A long-chain flavodoxin protects pseudomonas aeruginosa from oxidative stress and host bacterial clearance
(Public Library of Science (PLOS), 2014-02-13) Moyano, Alejandro José; Tobares, Romina Alín; Rizzi, Yanina S.; Krapp, Adriana R.; Mondotte, Juan Alberto; Bocco, José Luis; Saleh, Maria-Carla; Carrillo, Néstor; Smania, Andrea M.
Long-chain flavodoxins, ubiquitous electron shuttles containing flavin mononucleotide (FMN) as prosthetic group, play an important protective role against reactive oxygen species (ROS) in various microorganisms. Pseudomonas aeruginosa is an opportunistic pathogen which frequently has to face ROS toxicity in the environment as well as within the host. We identified a single ORF, hereafter referred to as fldP (for flavodoxin from P. aeruginosa), displaying the highest similarity in length, sequence identity and predicted secondary structure with typical long-chain flavodoxins. The gene was cloned and expressed in Escherichia coli. The recombinant product (FldP) could bind FMN and exhibited flavodoxin activity in vitro. Expression of fldP in P. aeruginosa was induced by oxidative stress conditions through an OxyR-independent mechanism, and an fldP-null mutant accumulated higher intracellular ROS levels and exhibited decreased tolerance to H2O2 toxicity compared to wild-type siblings. The mutant phenotype could be complemented by expression of a cyanobacterial flavodoxin. Overexpression of FldP in a mutT-deficient P. aeruginosa strain decreased H2O2-induced cell death and the hypermutability caused by DNA oxidative damage. FldP contributed to the survival of P. aeruginosa within cultured mammalian macrophages and in infected Drosophila melanogaster, which led in turn to accelerated death of the flies. Interestingly, the fldP gene is present in some but not all P. aeruginosa strains, constituting a component of the P. aeruginosa accessory genome. It is located in a genomic island as part of a self-regulated polycistronic operon containing a suite of stress-associated genes. The collected results indicate that the fldP gene encodes a long-chain flavodoxin, which protects the cell from oxidative stress, thereby expanding the capabilities of P. aeruginosa to thrive in hostile environments.
Acceso Abierto
A new IUPAC-consistent approach to the limit of detection in partial least-squares calibration
(American Chemical Society, 2014-07-10) Allegrini, Franco; Olivieri, Alejandro César

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