3D-QSAR/CoMFA Models as a Tool for Biocatalysis and Protein Engineering

The x-ray structure of an enzyme is taken into account, when available, as the reference model to explain catalytic activity and selectivity. Unfortunately, in most of the cases the structure is available only as apostructure, i.e. without the substrate bound to the active site, and it is strange to find many different enzyme-substrate complexes of a specific enzyme as crystals. Moreover this structure is not the "real" structure of the protein during catalysis as the crystal is stationary. In this paper we propose the use of CoMFA models to evaluate the differences betweenthe crystal and the real structure of the enzyme under reaction conditions. In addition to the stationary nature of a crystal, the experimental limitations of crystallographic techniques to obtain crystals in a fast and reliable manner, give a chance to the creation of CoMFA models by evaluating the easy to obtain catalytic properties of enzyme variants to provide information about the structural changes produced by the mutations. By means of the evaluation of different structures as substrates CoMFA models will not only provide information about the structure of the enzyme, but also about the flexibility and potential conformational changes of the substrate binding site

Clinical Presentation and Outcomes of Kawasaki Disease in Children from Latin America: A Multicenter Observational Study from the REKAMLATINA Network

Objetivos: Describir la presentación clínica, el manejo y los resultados de la enfermedad de Kawasaki (EK) en Latinoamérica y evaluar los indicadores pronósticos tempranos de aneurisma de la arteria coronaria (AAC). Diseño del estudio: Se realizó un estudio observacional basado en el registro de la EK en 64 centros pediátricos participantes de 19 países latinoamericanos de forma retrospectiva entre el 1 de enero de 2009 y el 31 de diciembre de 2013, y de forma prospectiva desde el 1 de junio de 2014 hasta el 31 de mayo de 2017. Se recopilaron datos demográficos, clínicos y de laboratorio iniciales. Se utilizó una regresión logística que incorporaba factores clínicos y la puntuación z máxima de la arteria coronaria en la presentación inicial (entre 10 días antes y 5 días después de la inmunoglobulina intravenosa [IGIV]) para desarrollar un modelo pronóstico de AAC durante el seguimiento (>5 días después de la IGIV). Resultados: De 1853 pacientes con EK, el ingreso tardío (>10 días tras el inicio de la fiebre) se produjo en el 16%, el 25% tuvo EK incompleta y el 11% fue resistente a la IGIV. Entre los 671 sujetos con puntuación z de la arteria coronaria notificada durante el seguimiento (mediana: 79 días; IQR: 36, 186), el 21% presentaba AAC, incluido un 4% con aneurismas gigantes. Un modelo pronóstico simple que utilizaba sólo una puntuación z de la arteria coronaria máxima ≥2,5 en la presentación inicial fue óptimo para predecir la AAC durante el seguimiento (área bajo la curva: 0,84; IC del 95%: 0,80, 0,88). Conclusiones: De nuestra población latinoamericana, la puntuación z de la arteria coronaria ≥2,5 en la presentación inicial fue el factor pronóstico más importante que precedió a la AAC durante el seguimiento. Estos resultados resaltan la importancia de la ecocardiografía temprana durante la presentación inicial de la EK. © 2023 Los autoresObjectives: To describe the clinical presentation, management, and outcomes of Kawasaki disease (KD) in Latin America and to evaluate early prognostic indicators of coronary artery aneurysm (CAA). Study design: An observational KD registry-based study was conducted in 64 participating pediatric centers across 19 Latin American countries retrospectively between January 1, 2009, and December 31, 2013, and prospectively from June 1, 2014, to May 31, 2017. Demographic and initial clinical and laboratory data were collected. Logistic regression incorporating clinical factors and maximum coronary artery z-score at initial presentation (between 10 days before and 5 days after intravenous immunoglobulin [IVIG]) was used to develop a prognostic model for CAA during follow-up (>5 days after IVIG). Results: Of 1853 patients with KD, delayed admission (>10 days after fever onset) occurred in 16%, 25% had incomplete KD, and 11% were resistant to IVIG. Among 671 subjects with reported coronary artery z-score during follow-up (median: 79 days; IQR: 36, 186), 21% had CAA, including 4% with giant aneurysms. A simple prognostic model utilizing only a maximum coronary artery z-score ≥2.5 at initial presentation was optimal to predict CAA during follow-up (area under the curve: 0.84; 95% CI: 0.80, 0.88). Conclusion: From our Latin American population, coronary artery z-score ≥2.5 at initial presentation was the most important prognostic factor preceding CAA during follow-up. These results highlight the importance of early echocardiography during the initial presentation of KD. © 2023 The Author(s

Evaluaci\uf3n de los resultados en pacientes sometidos a gastroyeyunoanastomosis por las T\ue9cnicas de Polya y Hofmeister. Hospital "Antonio Mar\ueda Pineda". Barquisimeto Julio 1997-Febrero 1999.

Desde 1997 a 1999, se realiz\uf3 un estudio descriptivo, transversal y ensayo cl\uednico en el Departamento de Cirug\ueda del Hospital "Antonio Mar\ueda Pineda" (HAMP), con el prop\uf3sito de evaluar los resultados en pacientes sometidos a gastroyeyunoanastomosis (GYA) por las t\ue9cnicas de Polya y de Hofmeister. Se incluye en el trabajo a todo paciente con gastrectom\ueda parcial m\ue1s vagotom\ueda troncular con indicaci\uf3n quir\ufargica de enfermedad \ufalcero-p\ue9ptica complicada, patolog\ueda neopl\ue1sica y traum\ue1tica. La GYA Polya se realiz\uf3 en 19 pacientes (46%) y la GYA Hofmeister en 22 pacientes (54%). En ambos grupos hubo un franco predominio del sexo masculino, 79% en el Polya y 73% en el Hofmeister. La edad promedio fue de 42,5 a\uf1os en el Polya y 52.3 a\uf1os en el Hofmeister. La indicaci\uf3n quir\ufargica m\ue1s frecuente fue la enfermedad ulcero-p\ue9ptica en la GYA polya (47%) y en la GYA Hofmeister fue el c\ue1ncer g\ue1strico (45%). En los dos grupos de estudios no hubo casos de s\uedndrome de Dumping y estenosis de la GYA. Al comparar los resultados el chi cuadrado (x\ub2=3D0), no es estad\uedsticamente significativo. Se concluye que en los pacientes sometidos a GYA el tipo de t\ue9cnica seleccionada (Hofmeister o Polya) no influyen en la frecuencia del s\uedndrome de Dumping y de estenosis anastom\uf3tica

High Throughput Screening and QSAR-3D/CoMFA: Useful Tools to Design Predictive Models of Substrate Specificity for

Dedicated to Dr. Mestres on his 65 th birthda

Chemoselective oxidation of primary alcohols to aldehydes with Gluconobacter oxydans

The production of aliphatic and aromatic aldehydes by oxidation of primary alcohols was achieved with Gluconobacter oxydans DSM 2343. The biotransformation was optimised studying the oxidation of 2-phenyl-1-ethanol to 2-phenylacetaldehyde. A high molar conversion (95% chromatographic conversion, 83% of isolated yield) was obtained using cells grown on glycerol as the main carbon source and directly used in the cultural medium after 24 h at 28°C, pH 4.5 and 5 g L−1 substrate concentration. The conversion of structurally different primary alcohols was performed under these conditions allowing the chemoselective production of aldehydes, sometimes with very good yields

Enantioselective monoreduction of different 1,2-diaryl-1,2-diketones catalysed by lyophilised whole cells from Pichia glucozyma

In this work we have studied the monoreduction of different 1,2-diaryl-ethanediones (benzils, 1) with lyophilised whole cells from Pichia glucozyma CBS 5766, using the diphenyl compound (benzil, 1a) as model substrate, and extended the enantioselective reduction to structurally different symmetric benzils for producing enantiomerically pure or enriched benzoins (alpha-hydroxyketones 2) in high yields and very short reaction times. In order to study the regio- and stereoselectivity of this biocatalyst, we examined the reduction of diaryldiketones formed from different aryl moieties, to obtain symmetric and asymmetric crossed-benzoins. This methodology is conducted under very mild reaction conditions (aqueous media with small amounts of DMSO for solubilising the substrates, T=28 degrees C), therefore constituting a green alternative compared to other reported procedures for obtaining homochiral benzoins. (C) 2008 Elsevier Ltd. All rights reserved

Versatile strategy for the synthesis of biotin-labelled glycans, their immobilization to establish a bioactive surface and interaction studies with a lectin on a biochip.

14 páginas, 10 figuras, 1 tabla -- PAGS nros. 633-646The emerging role of glycans as versatile biochemical signals in diverse aspects of cellular sociology calls for establishment of sensitive methods to monitor carbohydrate recognition by receptors such as lectins. Most of these techniques involve the immobilization of one of the binding partners on a surface, e.g. atomic force microscopy, glycan array and Surface Plasmon Resonance (SPR), hereby simulating cell surface presentation. Here, we report the synthesis of fluorescent glycoconjugates, with a functionalization strategy which avoids the frequently occurring ring opening at the reducing end for further immobilization on a surface or derivatization with biotin. In order to improve the versatility of these derivatized glycans for biological studies, a new approach for the synthesis of biotinylated and fluorescent glycans has also been realized. Finally, to illustrate their usefulness the neoglycoconjugates were immobilized on different surfaces, and the interaction analysis with a model lectin, the toxin from mistletoe, proved them to act as potent ligands, underscoring the merit of the presented synthetic approachThis work was supported by a Research Project of the MEC (Ministerio de Educación y Ciencia de España, CTQ2006-09052/BQU), a European Project (FP-62003-NMP-SMF-3, proposal 011774-2), an EC Marie Curie Research Training Network grant (MRTN-CT-2005-019561), the research initiative LMUexcellent and one of the authors (F. Javier Muñoz) thanks the MEC for a Ph.D. grant (MEC-FPU predoctoral fellowship AP2003-4820)Peer reviewe