Person: Hernáiz Gómez-Degano, María Josefa
Universidad Complutense de Madrid
Faculty / Institute
Química en Ciencias Farmacéuticas
Now showing 1 - 8 of 8
PublicationDesarrollo y elaboración de recursos didácticos on line para fomentar el autoaprendizaje interactivo y la autoevaluación en Química Farmacéutica con el apoyo del Campus Virtual(2018-06-30) Hoyos Vidal, Pilar; Hernáiz Gómez-Degano, María Josefa; Izquierdo Jiménez, Inmaculada; Alemán Sierra, Esther; García Oliva, Cecilia MaríaEn este Proyecto de Innovación Docente se ha pretendido de manera general optimizar las alternativas ofrecidas en el Campus Virtual, mediante el diseño, elaboración y evaluación de actividades didáticas on-line que permitan que el Aula Virtual se convierta en un apoyo activo en el proceso enseñanza-aprendizaje en la asignatura de Química Farmacéutica II. Se ha llevado a cabo la elaboración de cuestionarios interactivos de autoevaluación que permitan al alumno conocer la adecuación de los conocimientos adquiridos, y al docente poder realizar un seguimiento rápido de cada alumno. PublicationEfficient Synthesis of Muramic and Glucuronic Acid Glycodendrimers as Dengue Virus Antagonists(2020-02-03) Cabanillas, Alfredo H; Rumbero, Ángel; García Oliva, Cecilia María; Perona Requena, Almudena; Hernáiz Gómez-Degano, María Josefa; Hoyos Vidal, María PilarCarbohydrates are involved in many important pathological processes, such as bacterial and viral infections, by means of carbohydrate-protein interactions. Glycoconjugates with multiple carbohydrates are involved in multivalent interactions, thus increasing their binding strengths to proteins. In this work, we report the efficient synthesis of novel muramic and glucuronic acid glycodendrimers as potential Dengue virus antagonists. Aromatic scaffolds functionalized with a terminal ethynyl groups were coupled to muramic and glucuronic acid azides by click chemistry through optimized synthetic strategies to afford the desired glycodendrimers with high yields. Surface Plasmon Resonance studies have demonstrated that the compounds reported bind efficiently to the Dengue virus envelope protein. Molecular modelling studies were carried out to simulate and explain the binding observed. These studies confirm that efficient chemical synthesis of glycodendrimers can be brought about easily offering a versatile strategy to find new active compounds against Dengue virus. PublicationHighly Efficient and Sustainable Synthesis of Neoglycoproteins Using Galactosidases(American Chemical Society, 2020-03-02) Hoyos Vidal, María Pilar; Bavaro, Teodora; Perona Requena, Almudena; Rumbero, Angel; Tengattini, S; Terreni, Marco; Hernáiz Gómez-Degano, María Josefa; Hernáiz, MJOligosaccharides are a key component on glycoconjugates with biomedical applications. However, the investigation of more efficient and environmental protocols for their preparation carrying defined oligosaccharides remains a big challenge due to lack of access to structurally well-defined and functionalized oligosaccharides. In this work a highly sustainable and efficient chemoenzymatic synthesis of neo-glycoproteins in green solvents was studied. In particular, we described the preparation of new activated disaccharides useful for direct protein binding under mild reaction conditions, reducing the protection/activation steps commonly needed in the traditional synthetic routes. Thus, N-acetylglucosamine (GlcNAc) was functionalized with a thiocyanomethyl group at C-1 and employed for the first time as acceptor in the enzymatic synthesis of the disaccharide of interest using β-Gal-3 from Bacillus circulans and β-galactosidase from Escherichia coli. The use of biosolvents promotes a very important increase of the enzymatic activity in the synthesis of functionalized Gal-β-(1 → 6)-GlcNAc (95%) preventing hydrolytic activity with full regioselectivity. Furthermore, reaction scaling up and biosolvent recycling are feasible without losing catalytic action. The enzyme–substrate recognition and the effect of biosolvent over the galactosidases activity has been investigated and explained by computational modeling studies. The presence of C-1 thiocyanomethyl moiety strongly hindered the normal course of transglycosylation for β-Gal-3 afforded β(1 → 6) glyosidic linkage instead of β(1 → 3). Then, this functionalized disaccharide has been activated with imino methoxyethyl (IME) linker and conjugated to ribonuclease A (RNase A). The glycosylation of RNase A, with IME-disaccharide provided the corresponding neo-glycoprotein with 85% of yield. This work opens to a new, simple, and green way to synthesize innovative glycoconjugate vaccines. PublicationEnzymatic Synthesis and Molecular Modelling Studies of Rhamnose Esters Using Lipase from Pseudomonas stutzeri(MODI, 2022-02-17) Perona Requena, Almudena; García Oliva, Cecilia María; Rumbero, Ángel; Hoyos Vidal, María Pilar; Hernáiz Gómez-Degano, María Josefa; Hernáiz, MJ; Hernáiz Gómez-Degano, María JosefaRhamnolipids are becoming an important class of glycolipid biosurfactants. Herein, we describe for the first time the enzymatic synthesis of rhamnose fatty acid esters by the transesterification of rhamnose with fatty acid vinyl esters, using lipase from Pseudomonas stutzeri as a biocatalyst. The use of this lipase allows excellent catalytic activity in the synthesis of 4-O-acylrhamnose (99% conversion and full regioselectivity) after 3 h of reaction using tetrahydrofuran (THF) as the reaction media and an excess of vinyl laurate as the acyl donor. The role of reaction conditions, such as temperature, the substrates molar ratio, organic reaction medium and acyl donor chain-length, was studied. Optimum conditions were found using 35 °C, a molar ratio of 1:3 (rhamnose:acyldonor), solvents with a low logP value, and fatty acids with chain lengths from C4 to C18 as acyl donors. In hydrophilic solvents such as THF and acetone, conversions of up to 99–92% were achieved after 3 h of reaction. In a more sustainable solvent such as 2-methyl-THF (2-MeTHF), high conversions were also obtained (86%). Short and medium chain acyl donors (C4–C10) allowed maximum conversions after 3 h, and long chain acyl donors (C12–C18) required longer reactions (5 h) to get 99% conversions. Furthermore, scaled up reactions are feasible without losing catalytic action and regioselectivity. In order to explain enzyme regioselectivity and its ability to accommodate ester chains of different lengths, homology modelling, docking studies and molecular dynamic simulations were performed to explain the behaviour observed. PublicationTwo-step enzymatic strategy for the synthesis of a smart phenolic polymer and further immobilization of a β-galactosidase able to catalyze transglycosydation reaction(ELSEVIER, 2018-10) Levin, G.; Gómez, S.; Glodowsky, A.; Cascone, O.; Hernáiz Gómez-Degano, María Josefa; Hernáiz, MJA rapid and efficient enzymatic procedure for the preparation of an immobilized beta-galactosidase has been described. In a first step, soybean peroxidase was used to catalyze the polymerization of a strategically activated phenol (N-Succinimidyl 3-(4-hydroxyphenyl)propionate, known as Bolton-Hunter reagent). The phenolic support was directly employed for immobilizing S-galactosidase from Bacillus circulans (ATCC 31382, beta-Gal-3), giving rise to a new biocatalyst subsequently applied in the synthesis of a beta-galatodisaccharide (Gal-beta(1-3)-GlcNAc and Gal-beta(1-3)-GalNAc). The reaction proceeded with high conversion rates and total regioselectivity. Reusability assays were performed with the same reaction conditions finding that the immobilized enzyme retains about 55% of its activity after eight batches. Finally and based on our results, the two-step enzymatic procedure presented here is a good and green alternative to the preparation of carbohydrates with biological activities. PublicationExpanding the synthesis of a library of potent glucuronic acid glycodendrons for Dengue virus inhibition(ELSEVIER, 2023-12) Ramírez López, Pedro; Carlos Martínez; Alejandro Merchán; Perona Requena, Almudena; Hernáiz Gómez-Degano, María Josefa; Hernáiz, MJMultivalent glycodendrons are valuable tools to mimic many structural and functional features of cell-surface glycoconjugates and its focal position scaffolds represent important components to increase specificity and affinity. Previous work in our group described the preparation of a tetravalent glucuronic acid dendron that binds with good affinity to Dengue virus envelope protein (KD = 22 mu M). Herein, the chemical synthesis and binding analysis of a new library of potent glucuronic acid dendrons bearing different functional group at the focal position and different level of multivalency are described. Their chemical synthesis was performed sequentially in three stages and with good yields. Namely a) the chemical synthesis of the oligo and polyalkynyl scaffolds, b) assembling with fully protected glucuronic acid-based azide units by using a microwave assisted copper-catalysed azide-alkyne cycloaddition reaction and c) sequential deprotection of hydroxyl and carboxylic acid groups.Surface Plasmon Resonance studies have demonstrated that the valency and the focal position functional group exert influence on the interaction with Dengue virus envelope protein. Molecular modelling studies were carried out in order to understand the binding observed. This work reports an efficient glycodendrons chemical synthesis that provides appropriate focal position functional group and multivalence, that offer an easy and versatile strategy to find new active compounds against Dengue virus. PublicationCurrent challenges and future perspectives in sustainable mechanochemical transformations of carbohydrates(Royal Society of Chemistry, 2020) Hoyos Vidal, María Pilar; Perona Requena, Almudena; Ángeles Farrán; Hernáiz Gómez-Degano, María Josefa; Hernáiz, MJ; Royal Society of ChemistryThe use of mechanochemistry in carbohydrate chemistry is currently a growing field in which many new developments are being made because of its potential application in green methodologies. Ball milling (BM) is a promising eco-friendly technique with excellent characteristics that allows mostly solvent-free, faster and energy-efficient reactions. In this context, we provide in this perspective review a critical summary and discussion of the main known synthetic methods for carbohydrates based on mechanochemistry. The combination of the promising properties of mechanochemistry with carbohydrate reactions can be advantageous for setting strategies aligned with the green chemistry principles. PublicationAssembly of glycoamino acid building blocks: a new strategy for the straightforward synthesis of heparan sulfate mimics(Royal Society of London, 2018) Revuelta, Julia; Roberto Fuentes; Lagartera, Laura; Hernáiz Gómez-Degano, María Josefa; Bastida, Agatha; García-Junceda, Eduardo; Fernández-Mayoralas, Alfonso; Fernández-Mayoralas, Alfonso; Royal Society of LondonA new strategy that enables a modular straightforward synthesis of heparan sulfate oligosaccharide mimics by the assembly of simple glycoamino acid building blocks is described. The coupling between units is readily carried out by an amidation reaction. Several glycoamino acid oligomers were prepared and their interaction with the FGF2 protein was analyzed.