Person:
Hernáiz Gómez-Degano, María Josefa

First Name

María Josefa

Last Name

Hernáiz Gómez-Degano

URI

https://hdl.handle.net/20.500.14352/77506

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Química en Ciencias Farmacéuticas

Area

Química Orgánica

Identifiers

Full item page

Search Results

Now showing 1 - 10 of 25

Expanding the synthesis of a library of potent glucuronic acid glycodendrons for Dengue virus inhibition
(Bioorganic Chemistry, 2023) Ramírez López, Pedro; Martínez Espinosa, Carlos Antonio; Merchán, Alejandro ; Perona Requena, Almudena; Hernáiz Gómez-Degano, María Josefa
Multivalent 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 μM). 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.
Efficient Synthesis of Muramic and Glucuronic Acid Glycodendrimers as Dengue Virus Antagonists
(Chemistry - A European Journal, 2020) Cabanillas, Alfredo H; Rumbero, Ángel; García Oliva, Cecilia María; Perona Requena, Almudena; Hernáiz Gómez-Degano, María Josefa; Hoyos Vidal, María Pilar
Carbohydrates 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.
Enzymatic Synthesis and Molecular Modelling Studies of Rhamnose Esters Using Lipase from Pseudomonas stutzeri
(International Journal of Molecular Sciences, 2022) García Oliva, Cecilia María; Perona Requena, Almudena; Rumbero, Ángel; Hoyos Vidal, María Pilar; Hernáiz Gómez-Degano, María Josefa; Hernáiz Gómez-Degano, María Josefa
Rhamnolipids 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.
Development of sustainable synthesis of glucuronic acid glycodendrimers using ball milling and microwave-assisted CuAAC reaction
(New Journal of Chemistry, 2022) García Oliva, Cecilia María; Merchán, Alejandro ; Perona Requena, Almudena; Hoyos Vidal, María Pilar; Rumbero, Ángel ; Hernáiz Gómez-Degano, María Josefa
Two green strategies for copper-catalyzed azide-alkyne cycloaddition reaction based on two activation pathways, solvent free mechanochemistry and microwave irradiation using a recycable biosolvent, are reported for the synthesis of glucuronic acid glycodendrimers with good conversions (99%), the MW pathway being the ideal tool (90% yield in 90 min).
Two-step enzymatic strategy for the synthesis of a smart phenolic polymer and further immobilization of a β-galactosidase able to catalyze transglycosydation reaction
(International Journal of Biological Macromolecules, 2018) Levin, G.; Gómez, S.; Glodowsky, A.; Cascone, O.; Hernáiz Gómez-Degano, María Josefa; Hernáiz Gómez-Degano, María Josefa
A 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.
Synthesis of Glycodendrimers with Antiviral and Antibacterial Activity
(Chemistry - A European Journal, 2021) Hoyos Vidal, María Pilar; Juanes, Olga ; Perona Requena, Almudena; Rumbero, Ángel ; Hernáiz Gómez-Degano, María Josefa
Glycodendrimers are an important class of synthetic macromolecules that can be used to mimic many structural and functional features of cell‐surface glycoconjugates. Their carbohydrate moieties perform key important functions in bacterial and viral infections, often regulated by carbohydrate–protein interactions. Several studies have shown that the molecular structure, valency and spatial organisation of carbohydrate epitopes in glycoconjugates are key factors in the specificity and avidity of carbohydrate–protein interactions. Choosing the right glycodendrimers almost always helps to interfere with such interactions and blocks bacterial or viral adhesion and entry into host cells as an effective strategy to inhibit bacterial or viral infections. Herein, the state of the art in the design and synthesis of glycodendrimers employed for the development of anti‐adhesion therapy against bacterial and viral infections is described.
Assembly of glycoamino acid building blocks: a new strategy for the straightforward synthesis of heparan sulfate mimics
(Chemical Communications, 2018) Revuelta, Julia; Fuentes, Roberto ; Lagartera, Laura; Hernáiz Gómez-Degano, María Josefa; Bastida, Agatha; García-Junceda, Eduardo; Fernández-Mayoralas, Alfonso; Fernández-Mayoralas, Alfonso; Royal Society of London
A 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.
Highly Efficient and Sustainable Synthesis of Neoglycoproteins Using Galactosidases
(ACS Sustainable Chemistry and Engineering, 2020) Hoyos Vidal, María Pilar; Bavaro, Teodora; Perona Requena, Almudena; Rumbero, Ángel; Tengattini, S. ; Terreni, Marco; Hernáiz Gómez-Degano, María Josefa; Hernáiz Gómez-Degano, María Josefa
Oligosaccharides 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.
Expanding the synthesis of a library of potent glucuronic acid glycodendrons for Dengue virus inhibition
(Bioorganic Chemistry, 2023) Ramírez López, Pedro; Martínez Espinosa, Carlos Antonio; Merchán, Alejandro ; Perona Requena, Almudena; Hernáiz Gómez-Degano, María Josefa; Hernáiz Gómez-Degano, María Josefa
Multivalent 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.
Highly Efficient and Sustainable Synthesis of Neoglycoproteins Using Galactosidases
(ACS Sustanaible Chemistry & Engineering, 2020) Hoyos Vidal, María Pilar; Perona Requena, Almudena; Hernáiz Gómez-Degano, María Josefa; Bavaro, Teodora; Rumbero Sánchez, Ángel; Tengattini, Sara; Terreni, Marco; Hernáiz Gómez-Degano, María Josefa
Oligosaccharides 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.