Publicaciones

Esta sección incluye una lista de los últimos artículos científicos del IPNA publicados en revistas incluidas en el Science Citation Index (SCI).

En DIGITAL.CSIC, repositorio institucional del CSIC, pueden encontrar el listado completo de artículos científicos desde 1962, así como otras colecciones de interés como congresos, tesis, libros, material divulgativo, etc. del centro. El objetivo de DIGITAL.CSIC es organizar, preservar y difundir en acceso abierto los resultados de nuestra investigación.

En el repositorio institucional del CSIC, pueden encontrar el listado completo de artículos científicos, así como otras colecciones de interés como congresos, tesis, libros, material divulgativo, etc.

Ir a Digital - CSIC

 

Análisis de la Producción Científica del IPNA 2014-2019: análisis bibliométrico realizado a partir de datos recogidos en Scopus y Web of Science.

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Digital CSIC

The Nitration of Proteins, Lipids and DNA by Peroxynitrite Derivatives-Chemistry Involved and Biological Relevance

In recent years, much interest has been generated by the idea that nitrosative stress plays a role in the aetiology of human diseases, such as atherosclerosis, inflammation, cancer, and neurological diseases. The chemical changes mediated by reactive nitrogen species (RNS) are detrimental to cell function, because they can cause nitration, which can alter the structures of cellular proteins, DNA, and lipids, and hence, impair their normal function. One of the most potent biological nitrosative agents is peroxynitrite (ONOO¯), which is produced when nitric oxide (*NO) and superoxide (*O2¯) are combined at extremely rapid rates. Considering the plethora of oxidations by peroxynitrite, this makes peroxynitrite the most prevalent nitrating species responsible for protein, DNA, and lipids nitration in vivo. There is biochemical evidence to suggest that the interactions of the radicals NO and superoxide result in the formation of a redox system, which includes the reactions of nitrosation and nitration, and is a component of the complex cellular signalling network. However, the chemistry involved in the nitration process with peroxynitrite derivatives is poorly understood, particularly for biological molecules, such as DNA, proteins, and lipids. Here, we review the processes involved in the nitration of biomolecules, and provide a mechanistic explanation for the chemical reactions of NOS and nitrosative stress. This study reveals that these processes are based on a surprisingly simple and straightforward chemistry, with a fascinating influence on cellular physiology and pathology.

Pérez de Lastra, José Manuel; Andrés Juan, Celia; Plou Gasca, Francisco José; Pérez-Lebeña, Eduardo.

Stresses 2(1): 53-64 (2022)
DOIDigital.CSIC

Free-Radical Epimerization of D- into L-C-(glycosyl)methanol Compounds Using 1,5-Hydrogen Atom Transfer Reaction

A simple epimerization of C-(α-D-Gly p )methanol into C-(β-L-Gly p )methanol compounds is described. The radical sequence involved homolytic cleavage of the C5–H bond by 1,5-hydrogen atom transfer promoted by the 1’-O-yl radical and subsequent hydride addition with inversion of configuration. This methodology allows the preparation of rare C-(β-L-Ido p )-, C-(β-L-Altp)-, C-(β-L-Gulp)-, C-(β-L-Allp)methanol glycosides starting from carbohydrates of the D-series. It can also be applied to transform L- into D-configured C-glycosyl compounds, as illustrated by the formation of C-(β-D-6dGulp)- and C-(β-D-6dAltp)methanol from readily accessible L-rhamno and L-fuco analogs, respectively. In further development of this procedure compounds with C-(β-L-Araf)- and C-(β-L-5dRibf)methanol structures have also been synthesized. The alkoxyl radicals were generated by reaction of the corresponding N-alkoxyphthalimides with nBu3SnH(D) and in comparative terms, by visible light-photocatalysis using the Hantzsch ester/fac-Ir(ppy)3 procedure. The influence of the sugar ring conformation and the electronegativity of the substituents on the stereochemical outcome will be addressed.

Montes, Adrián S.; León, Elisa I.; Martín, Ángeles; Pérez-Martín, Inés; Suárez, Ernesto

European Journal of Organic Chemistry: 1-27 (2022)
DOIDigital.CSIC

Osteoprotective effect of the marine alkaloid norzoanthamine on an osteoporosis model in ovariectomized rat

Norzoanthamine (NZ), an alkaloid that has been isolated from the marine cnidiaria Zoanthus sp., has been shown an interesting anti-osteoporotic activity. Although its mechanism of action is not yet clear, it seems that it is different from those of currently used drugs making it particularly interesting. Previous studies have been carried out mostly in vitro. Herein, we present an in vivo study that allows to check the real potential of NZ as a protector substance by direct application into ovariectomized rat bone using a sustained delivery system. Histological and histomorphometric results in ovariectomized rats showed higher bone quality as a result of greater number of trabeculae and osteogenic activity in the group implanted with NZ, compared to controls. In contrast with the untreated controls, NZ-treated groups showed a balanced osteoblast/osteoclast number ratio, similar to that found in the normal bone. These results suggest that NZ could be useful as adjunct to other osteoporosis treatments, but probably its main therapeutic role would be as preventive therapy against bone deterioration.

García-García, Patricia; Reyes, Ricardo; Évora, Carmen; Delgado, Araceli; Fernández, José J.; Hernández Daranas, Antonio.

Biomedicine and Pharmacotherapy 147, 112631: 1-9 (2022)
DOIDigital.CSIC

ConCiencia Histórica: la arqueología comunitaria como medio para la coconstrucción de conocimiento en un entorno rural

En la última década la arqueología comunitaria ha experimentado un importante crecimiento en España. Este crecimiento se explica, en algunos casos, por la necesaria reinvención de los arqueólogos tras el colapso de la profesión ligada a la crisis económica que se inicia en el 2009; en otros casos está relacionado con la cada vez más demandada divulgación científica dentro del marco de la transferencia de conocimiento. Esto ha supuesto la realización de programas didácticos paralelos a los proyectos de investigación arqueológica. En este artículo presentamos la experiencia de arqueología comunitaria realizada por el grupo de investigación Llabor que lleva a cabo los trabajos arqueológicos en el yacimiento de Vigaña, el colegio público y el Ayuntamiento de Balmonte de Miranda. Un ensayo que puede ser un buen ejemplo para desarrollar experiencias similares en ámbitos rurales.

Fernández Mier, Margarita; López Gómez, Pablo; Peláez Álvarez, Nuria; Domínguez Álvarez, Teresa; Menéndez Martínez, María; Rodríguez Pérez, Santiago; Villa Varela, Aida; Alonso-González, Pablo; Fernández, Xosé Antón Ambás; Ilesies Fernández, Ramsés; Álvarez Alba, María Dolores; Fernández Fernández, Jesús; Fernández Villamil, Amaya.

Si te dedicas a la ciencia, ¡divúlgala! (2): 35-54 (2021)
Digital.CSIC

Antibodies targeting enzyme inhibition as potential tools for research and drug development

Antibodies have transformed biomedical research and are now being used for different experimental applications. Generally, the interaction of enzymes with their specific antibodies can lead to a reduction in their enzymatic activity. The effect of the antibody is dependent on its narrow i.e. the regions of the enzyme to which it is directed. The mechanism of this inhibition is rarely a direct combination of the antibodies with the catalytic site, but is rather due to steric hindrance, barring the substrate access to the active site. In several systems, however, the interaction with the antibody induces conformational changes on the enzyme that can either inhibit or enhance its catalytic activity. The extent of enzyme inhibition or enhancement is, therefore, a reflection of the nature and distribution of the various antigenic determinants on the enzyme molecule. Currently, the mode of action of many enzymes has been elucidated at the molecular level. We here review the molecular mechanisms and recent trends by which antibodies inhibit the catalytic activity of enzymes and provide examples of how specific antibodies can be useful for the neutralization of biologically active molecules.

Pérez de Lastra, José Manuel; Baca González, Victoria; González-Acosta, Sergio; Asensio Calavia, Patricia; Otazo-Pérez, Andrea; Morales-delaNuez, Antonio.

Biomolecular Concepts 12(1): 215–232 (2021)
DOIDigital.CSIC

Antiamoeboid activity of squamins C–F, cyclooctapeptides from Annona globifora

Free-living amoebae of Acanthamoeba spp. are causative agents of human infections such as granulomatous amoebic encephalitis (GAE) and Acanthamoeba keratitis (AK). The exploration of innovative chemical entities from natural sources that induce intrinsic apoptotic pathway or a Programmed Cell Death (PCD) in Acanthamoeba protozoa is essential to develop new therapeutic strategies. In this work, the antiamoeboid activity of squamins C–F (1–4), four cyclooctapeptides isolated from Annona globiflora was tested in vitro against Acanthamoeba castellanii Neff, A. polyphaga, A. quina, and A. griffini, and a structure–activity relationship was also established. The most sensitive strain against all tested cyclooctapeptides was A. castellanii Neff being the R conformers of the S-oxo-methionine residue, squamins D (2) and F (4), the most active against the trophozoite stage. It is remarkable that all four peptides showed no cytotoxic effects against murine macrophages cell line J774A.1. The analysis of the mode of action of squamins C–F against A. castellanii indicate that these cyclopeptides induced the mechanisms of programmed cell death (PCD). All peptides trigger mitochondrial damages, significant inhibition of ATP production compared to the negative control, chromatin condensation and slight damages in membrane that affects its permeability despite it conserves integrity at the IC90 for 24 h. An increase in reactive oxygen species (ROS) was observed in all cases.

Rodríguez-Expósito, Rubén L.; Sosa-Rueda, Javier; Reyes-Batlle, María; Sifaoui, Inés; Cen-Pacheco, Francisco; Hernández Daranas, Antonio; Díaz-Marrero, Ana R.; Piñero, José E.; Fernández, José J.; Lorenzo-Morales, Jacob

International Journal for Parasitology: Drugs and Drug Resistance 17: 67-79 (2021)
DOIDigital.CSIC

Invasive snake causes massive reduction of all endemic herpetofauna on Gran Canaria

Invasive snakes represent a serious threat to island biodiversity, being responsible for far-reaching impacts that are noticeably understudied, particularly regarding native reptiles. We analysed the impact of the invasive California kingsnake, Lampropeltis californiae—recently introduced in the Canary Islands—on the abundance of all endemic herpetofauna of the island of Gran Canaria. We quantified the density in invaded and uninvaded sites for the Gran Canaria giant lizard, Gallotia stehlini, the Gran Canaria skink, Chalcides sexlineatus, and Boettger's wall gecko, Tarentola boettgeri. We used spatially explicit capture-recapture and distance-sampling methods for G. stehlini and active searches under rocks for the abundance of the other two reptiles. The abundance of all species was lower in invaded sites, with a reduction in the number of individuals greater than 90% for G. stehlini, greater than 80% for C. sexlineatus and greater than 50% for T. boettgeri in invaded sites. Our results illustrate the severe impact of L. californiae on the endemic herpetofauna of Gran Canaria and highlight the need for strengthened measures to manage this invasion. We also provide further evidence of the negative consequences of invasive snakes on island reptiles and emphasize the need for further research on this matter on islands worldwide.

Piquet, Julien C.; López-Darias, Marta

Proceedings of the Royal Society B: Biological Sciences 288(1964): 20211939 (2021)
DOIDigital.CSIC

Site-selective modification of peptide backbones

The site-selective modification of peptide backbones allows an outstanding fine-tuning of peptide conformation, folding ability, and physico-chemical and biological properties. However, to achieve selectivity in the core of these biopolymers is challenging. In the last few years, many advances towards this goal have been developed. This review addresses the selective modification of Cα- and N-positions, from the use of “customizable units” to the residue-directed introduction of substituents. The site-selective modification of the peptide bond, i.e. the formation of thioamides or heterocycles, which alters backbone rigidity and ability to form hydrogen bonds or recognition by enzymes, is also described. Moreover, not only the modifications in internal backbone positions, but also in the N- and C-termini are discussed. In addition to chemical methodologies, the review addresses some reactions, catalyzed by natural or engineered enzymes, that afford unprecedent regio- and stereoselectivity in backbone modifications.

Boto, Alicia; González Martín, Concepción C.; Hernández, Dácil; Romero-Estudillo, Iván; Saavedra, Carlos J.

Organic Chemistry Frontiers 8(23): 6720 - 6759 (2021)
DOIDigital.CSIC

Relationship Between Exposure to Sulphur Dioxide Air Pollution, White Cell Inflammatory Biomarkers and Enzymatic Infarct Size in Patients With ST-segment Elevation Acute Coronary Syndromes

Aims: To analyse the relationship among air pollutants, markers of inflammation and infarct size in patients with acute coronary syndrome (ACS). Methods: This was a prospective analysis of consecutive patients admitted to hospital because of ACS. Cardiac biomarkers were drawn. The daily mean values of the air pollutants from the day before until 7 days before admission were analysed. The study population was stratified according to infarct size, based on median peak troponin value. Results: Patients were divided into two groups of 108 subjects each, according to median peak troponin value. Patients with extensive MIs had a higher neutrophil:lymphocyte ratio and leukocyte and neutrophil counts than patients with smaller MIs. In addition, they were exposed to higher concentrations of sulphur dioxide (9.7 ± 4.1 versus 8.4 ± 3.1 μg/m3 ; p=0.009) and lower concentrations of ozone (33.8 ± 13.7 versus 38.6 ± 14.5 μg/m3 ; p=0.014). Multivariate analysis showed that sulphur dioxide levels (OR 1.12; 95% CI [1.031–1.21]; p=0.007) and neutrophil/lymphocyte ratio (OR 1.08; 95% CI [1.011–1.17]; p=0.024) were independent predictors of infarct size. Conclusion: Patients with extensive MIs had higher white cell inflammatory levels and had been exposed to higher sulphur dioxide concentrations in the ambient air.

Díaz-Chirón, Laura; Negral, Luis; Megido, Laura; Suárez-Peña, Beatriz; Domínguez-Rodríguez, Alberto; Rodríguez, Sergio; Abreu-González, Pedro; Pascual, Isaac; Moris, César; Avanzas, Pablo

European Cardiology Review 16:e50 (2021)
DOIDigital.CSIC

Intramolecular Metal-free C(sp3)-H Activation Enables a Selective Mono O-Debenzylation of Fully Protected Aminosugars

Carbamate-bearing benzylated aminosugars undergo an I2/I(III)-promoted intramolecular hydrogen atom transfer (IHAT) followed by a nucleophilic attack to provide polycyclic structures. Thus, suitably positioned benzyl ethers are surgically oxidized into the corresponding mixed N/O-benzylidene acetals, which can be conveniently deprotected under mild acidic conditions to grant access to selectively O-deprotected aminosugars amenable for further derivatization. The scope of this strategy has been proven with a battery of furanosic and pyranosic scaffolds. Preliminary mechanistic studies, including Hammett LFER and KIE analyses, support a reaction pathway with the nucleophilic cyclization as the rate-determining step.

Santana, Andrés G.; Herrera, Antonio J.; González Martín, Concepción C.

Journal of Organic Chemistry 86(23): 16736–16752 (2021)
DOIDigital.CSIC