Síntesis de nuevos catalizadores basados en prolina y evaluación de su actividad en la reacción aldólica

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura: 20-01-201

Optimization of a class of tryptophan dendrimers that inhibit HIV replication leads to a selective, specific, and low-nanomolar inhibitor of clinical isolates of enterovirus A71

Tryptophan dendrimers that inhibit HIV replication by binding to the HIV envelope glycoproteins gp120 and gp41 have unexpectedly also proven to be potent, specific, and selective inhibitors of the replication of the unrelated enterovirus A71. Dendrimer 12, a consensus compound that was synthesized on the basis of the structure-activity relationship analysis of this series, is 3-fold more potent against the BrCr lab strain and, surprisingly, inhibits a large panel of clinical isolates in the low-nanomolar/high-picomolar range.This work has been supported by the Spanish MINECO (Project SAF2012-39760-C02-01, cofinanced by the FEDER program; Plan Nacional de Cooperación Público-Privada; and Subprograma INNPACTO IPT-2012-0213-060000, cofinanced by the FEDER program) and the Comunidad de Madrid (BIPEDD2-CM-S2010/BMD-2457). This work was also funded by EU FP7 (FP7/2007-2013) Project EUVIRNA under Grant408 Agreement 264286 by EU FP7 SILVER (Contract HEALTH-F3-2010- 260644), a grant from the Belgian Interuniversity Attraction Poles (IAP) Phase VII–P7/45 (BELVIR), and the EU FP7 Industry-Academia Partnerships and Pathways Project AIROPICO. The Spanish MEC/MINECO is also acknowledged for a grant to E.R.-B. L.S. was funded by China Scholarship Council (CSC) Grant 201403250056. We also acknowledge Charlotte Vanderheydt for help with the processing of the antiviral data.Peer Reviewe

Tryptophan dendrimers that inhibit HIV replication, prevent virus entry and bind to the HIV envelope glycoproteins gp120 and gp41

Dendrimers containing from 9 to 18 tryptophan residues at the peryphery have been efficiently synthesized and tested against HIV replication. These compounds inhibit an early step of the replicative cycle of HIV, presumably virus entry into its target cell. Our data suggest that HIV inhibition can be achieved by the preferred interaction of the compounds herein described with glycoproteins gp120 and gp41 of the HIV envelope preventing interaction between HIV and the (co)receptors present on the host cells. The results obtained so far indicate that 9 tryptophan residues on the periphery are sufficient for efficient gp120/gp41 binding and anti-HIV activity.This work has been supported by the Spanish MINECO (project SAF2012-39760-C02, co-financed by the FEDER programme); Plan Nacional de Cooperacion Público-Privada, subprograma INNPACTO (project IPT-2012-0213-060000, co-financed by the FEDER programme), the Comunidad de Madrid (BIPEDD2-CM-S2010/BMDE2457) and by “The Centers of Excellence” of the K.U.Leuven (EF-05/ 15 and PF-10/18). The Spanish MICINN/MINECO are also acknowledged for a grant to E. Rivero-BucetaPeer Reviewe

Job satisfaction: Analysis of predictor variables in a sample of healthcare proffessionals, in Specialty Care, of a sanitary area of the Comunidad de Madrid

Artículos originales[ES] Este trabajo presenta los resultados del estudio de satisfacción laboral realizado a una muestra de 873 trabajadores de la sanidad pública, mediante aplicación de un cuestionario ad hoc, cuya estructura se presenta. A partir de estos resultados, se analizan las variables con capacidad predictiva sobre la satisfacción laboral general en la muestra. El objetivo es la búsqueda de un modelo válido que permita el planteamiento de estrategias preventivas y de intervención en el contexto laboral analizado, como vía para aumentar los niveles de satisfacción y salud laboral. [EN] This work presents the result of a study in job satisfaction performed to a sample of 873 workers of public healthcare by applying an ad hoc questionnaire whose structure will be presented here too. With the support of these results, the variables with predictor potential over the general sample job satisfaction will be analyzed. The main aim of this work is the finding of a valid model that allows the development of prevention and intervention strategies in the job context analyzed, as a way to increase job satisfaction and public health.N

Bifidobacterial ß-galactosidase-mediated production of galacto-oligosaccharides: structural and preliminary functional assessments

This work was sponsored by FrieslandCampina. DS, VA, and FB are members of APC Microbiome Ireland, which is a research center funded by Science Foundation Ireland (SFI), through the Irish Government’s National Development Plan. The authors and their work were supported by SFI (Grant SFI/12/RC/2273), FEMS Research Grant FEMS-RG-2016-0103 and project AGL2017-84614-C2-1-R funded by the Spanish Ministry of Economy, Industry and Competitiveness. OH-H has received funding from the European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska- Curie grant agreement no. 843950

Anti-HIV-1 activity of a tripodal receptor that recognizes mannose oligomers

The glycoprotein gp120 of the HIV-1 viral envelope has a high content in mannose residues, particularly ¿-1,2-mannose oligomers. Compounds that interact with these high-mannose type glycans may disturb the interaction between gp120 and its (co)receptors and are considered potential anti-HIV agents. Previously, we demonstrated that a tripodal receptor (1), with a central scaffold of 1,3,5-triethylbenzene substituted with three 2,3,4-trihydroxybenzoyl groups, selectively recognizes ¿-1,2-mannose polysaccharides. Here we present additional studies to determine the anti-HIV-1 activity and the mechanism of antiviral activity of this compound. Our studies indicate that 1 shows anti-HIV-1 activity in the low micromolar range and has pronounced gp120 binding and HIV-1 integrase inhibitory capacity. However, gp120 binding rather than integrase inhibition seems to be the primary mechanism of antiviral activity of 1.The Spanish MICINN/MINECO (Project: SAF 201239760-C02-01, co-financed by the FEDER programme); Plan Nacional de Cooperación Público-Privada. Subprograma INNPACTO (IPT-2012-0213-060000, co-financed by the FEDER programme) and the Comunidad de Madrid (BIPEDD2-CM-S2010/BMD-2457) are acknowledged for fi nancial support. The Spanish ICINN/MINECCO is also acknowledged for a grant to E. Rivero-Buceta. We thank Leentje Persoons, Frieda De Meyer, Leen Ingels, Stijn Delmotte, Katrien Geerts, and Inge Vliegen for excellent technical assistance. Financial support of KU Leuven (GOA 10/14; PF 10/18) and the FWO (G-0528.12N) was provided for the antiviral experiments. The integrase studies were supported by the Center for Cancer Research, the Intramural Program of the National Cancer Institute,NIH (Z01-BC 007333).Peer Reviewe

Substrate channelling in an engineered bifunctional aldolase/kinase enzyme confers catalytic advantage for C–C bond formation

A new bifunctional enzyme that displays both aldolase and kinase activities has been designed and successfully used in the synthesis of aldol adducts, employing DHA as initial donor,with an increase in the reaction rate of 20-fold over the parent enzymes, which can be interpreted in terms of substrate channelling.Peer reviewe

Proline-cyclodextrin conjugates: Synthesis and evaluation as catalysts for aldol reaction in water

The synthesis of six conjugates of l-proline and β-cyclodextrin and their evaluation as catalysts of aldol reaction in water are described. The results indicated that the nature of the linker between proline and β-cyclodextrin is important for catalytic activity; the one with the most flexible linker gave the best results. Inhibition experiments showed that the cavity of β-cyclodextrin plays a role in the catalysis. Permethylation of the cyclodextrin hydroxyl groups led to higher conversion rates.Peer Reviewe

Activated α, β-Unsaturated Aldehydes as Substrate of Dihydroxyacetone Phosphate (DHAP)-Dependent Aldolases in the Context of a Multienzyme System

Published in: Advanced Synthesis & Catalysis, Volume 351, Issue 17, Date: November 2009, Pages: 2967-2975.The utility for carbon-carbon bond formation of a multienzyme system composed of recombinant dihydroxyacetone kinase (DHAK) from Citrobacter freundii, the fructose bisphosphate aldolase from rabbit muscle (RAMA) and acetate kinase (AK) for adenosine triphosphate (ATP) regeneration has been studied. Several aldehydes with great structural diversity, including three ,-unsaturated aldehydes, have been analysed as acceptor substrates. It was found that ,-unsaturated aldehydes bearing an electron-withdrawing group in the position to the double bond with a trans configuration are good acceptors for RAMA in this multienzyme system. The aldol reaction proceeds with excellent D-threo enantioselectivity and the aldol adduct is obtained in good overall yield. The L-threo and D-erythro enantiomers are also accessible from rhamnulose 1-phosphate aldolase (Rha-1PA) and fuculose 1-phosphate aldolase (Fuc-1PA) catalysed reactions, respectively.Funded by: Spanish Ministerio de Ciencia e Innovación; Grant Number: CTQ2007-67403/BQU Comunidad de MadridPeer reviewe