A5071030408- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- RNA Interference and Gene Delivery
- Microbial Metabolites in Food Biotechnology
- Lysosomal Storage Disorders Research
- Advanced biosensing and bioanalysis techniques
- Enzyme Production and Characterization
- Chemical Synthesis and Analysis
- Polyamine Metabolism and Applications
- Diet, Metabolism, and Disease
- Supramolecular Self-Assembly in Materials
- DNA and Nucleic Acid Chemistry
- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Enzyme Catalysis and Immobilization
- Biochemical and Molecular Research
- Nanoparticle-Based Drug Delivery
- Drug Solubulity and Delivery Systems
- Synthesis of Organic Compounds
- Trypanosoma species research and implications
- Synthesis and Characterization of Heterocyclic Compounds
- Proteoglycans and glycosaminoglycans research
- Dendrimers and Hyperbranched Polymers
- Educational Outcomes and Influences
- Bacteriophages and microbial interactions
Centro de Investigaciones Científicas Isla de la Cartuja
2015-2024
Instituto de Investigaciones Químicas
2015-2024
Universidad de Sevilla
2015-2024
University of Alicante
2015-2022
Arkema (United Kingdom)
2020
IVI Sevilla Clinic
2014-2020
Consejo Superior de Investigaciones Científicas
2001-2020
Valencian International University
2017
University of Bío-Bío
2017
Universidad de Alcalá
2008-2015
Dendritic β-cyclodextrin (βCD) derivatives bearing multivalent mannosyl ligands have been prepared and assessed for their binding efficiency toward the tetrameric plant lectin concanavalin A (Con A) a mammalian mannose/fucose specific cell surface receptor from macrophages. The synthetic strategy exploits reactivity between isothiocyanate amine functionalities high-yielding assembly via thioureido links of various building blocks, including host, spacer, branching, carbohydrate ligand...
Recent advancements and future outlook on pharmacological chaperones for lysosomal storage disorders using glycomimetics are discussed.
Abstract Gaucher disease (GD) is caused by mutations in the GBA1 gene, which encodes lysosomal β-glucocerebrosidase. Homozygosity for L444P mutation associated with high risk of neurological manifestations are not improved enzyme replacement therapy. Alternatively, pharmacological chaperones (PCs) capable restoring correct folding and trafficking mutant represent promising alternative therapies.Here, we report on how affects mitochondrial function primary fibroblast derived from GD patients....
Abstract Viruses represent a paradigmatic example of multicomponent, self‐organized supramolecular systems specialized in the delivery and replication their genetic material. Mimicking functioning by artificial synthetic molecules represents fantastic challenge that will lead to future development gene therapy. This is only possible if general approaches towards construction nanoscale vehicles for DNA are developed key rules governing capacity compact material its active transport/delivery...
A molecular-diversity-oriented approach for the preparation of well-defined polycationic amphiphilic cyclodextrins (paCDs) as gene-delivery systems is reported. The synthetic strategy takes advantage differential reactivity primary versus secondary hydroxyl groups on CD torus to regioselectively decorate each rim with cationic elements and lipophilic tails, respectively. Both charge density hydrophobic-hydrophilic balance can be finely tuned in a highly symmetrical architecture that...
Abstract Concerted functioning of lectins and carbohydrate‐processing enzymes, mainly glycosidases, is essential in maintaining life. It was commonly assumed that the mechanisms by which each class protein recognizes their cognate sugar partners are intrinsically different: multivalency a characteristic feature carbohydrate–lectin interactions, whereas glycosidases bind to substrates or substrate‐analogue inhibitors monovalent form. Recent observations on glycosidase inhibitory potential...
Son escasos los estudios que analizan la relación entre conducta agresiva e inteligencia emocional. Este estudio examina emocional rasgo y componentes motor (agresividad física agresividad verbal), cognitivo (hostilidad) afectivo/emocional (ira) de agresiva. El Trait Emotional Intelligence Questionnaire-Adolescents Short Form (TEIQue-ASF) el Aggression Questionnaire version (AQ-S) fueron administrados a una muestra 314 adolescentes (52.5% chicos) 12 17 años. Los resultados indicaron con...
Monodisperse facial amphiphiles consisting of a β-cyclodextrin (βCD) platform exposing multivalent display cationic groups at the primary rim and bearing hydrophobic chains secondary oxygens have been prepared by implementing two very robust "click" methodologies, namely cuprous cation-catalyzed azide-alkyne cycloaddition (CuAAC) thiourea-forming reaction. Most interestingly, use solid-supported Cu(I) catalysts was found to be well suited for multiple CuAAC while facilitating purification...
Gaucher's disease (GD) is caused by mutations in the GBA1 gene, which encodes acid-β-glucosidase, an enzyme involved degradation of complex sphingolipids. While non-neuronopathic aspects can be treated with replacement therapy (ERT), early-onset neuronopathic form currently lacks therapeutic options and lethal. We have developed induced pluripotent stem cell (iPSc) model GD. Dermal fibroblasts a patient P.[LEU444PRO];[GLY202ARG] genotype were transfected loxP-flanked polycistronic...
Lysosomal β-galactosidase (β-Gal) deficiency causes a group of disorders that include neuronopathic GM1 gangliosidosis and non-neuronopathic Morquio B disease. We have previously proposed the use small molecule ligands β-Gal as pharmacological chaperones (PCs) for treatment brain pathology. Although it is still under development, PC therapy has yielded promising preclinical results in several lysosomal diseases. In this study, we evaluated effect bicyclic 1-deoxygalactonojirimycin (DGJ)...
Glycosidases are key enzymes in metabolism, pathogenic/antipathogenic mechanisms and normal cellular functions. Recently, a novel approach for glycosidase inhibition that conveys multivalent glycomimetic conjugates has emerged. Many questions regarding the mechanism(s) of enzyme remain unanswered. Herein we report synthesis collection homo- heterovalent glyco(mimetic)-fullerenes purposely conceived probing contribution non-catalytic pockets glysosidases to inhibitory effect. Their affinities...
Abstract A general approach is reported for the design of small‐molecule competitive inhibitors lysosomal glycosidases programmed to 1) promote correct folding mutant enzymes at endoplasmic reticulum, 2) facilitate trafficking, and 3) undergo dissociation self‐inactivation lysosome. The strategy based on incorporation an orthoester segment into iminosugar conjugates switch nature aglycone moiety from hydrophobic hydrophilic in pH 7 5 window, which has a dramatic effect enzyme binding...
Results obtained over the past decade towards preparation of multitopic carbohydrate architectures combining molecular inclusion capabilities cyclomaltooligosaccharide receptors (cyclodextrins, CDs) and recognition properties saccharide ligands biological are discussed. The potential these new sugar-based "intelligent" transporters for site specific delivery therapeutics is outlined.
Gaucher disease (GD), the most prevalent lysosomal storage disorder, is caused by mutations of beta-glucosidase (acid beta-Glu, beta-glucocerebrosidase); these result in protein misfolding. Some inhibitors this enzyme, such as iminosugar glucomimetic N-(n-nonyl)-1-deoxynojirimycin (NN-DNJ), are known to bind active site and stabilize proper folding for catalytic form, acting "chemical chaperones" that facilitate transport maturation acid beta-Glu. Recently, bicyclic nojirimycin (NJ)...
Self-assembled cyclodextrin (CD)–DNA nanoparticles (CDplexes) exhibiting transfection efficiencies significantly higher than PEI-based polyplexes have been prepared from homogeneous seven-fold symmetric polyaminothiourea amphiphiles constructed on a β-cyclodextrin scaffold.
sp2-Iminosugar-type castanospermine analogues bearing an α-configured N-, S-, or C-linked pseudoanomeric group have been designed as selective inhibitors of the neutral α-glucosidases involved in N-glycoprotein processing; evaluation breast cancer cell growth indicated a significant antiproliferative potential that was dependent on nature group.
Gene delivery systems based on the β-cyclodextrin scaffold have been synthesized by combining copper(I)-catalyzed azide-alkyne coupling ("click chemistry") and an efficient acylation method of secondary hydroxyls; molecular flexibility, charge density hydrophobic-hydrophilic balance are critical parameters that can be fine-tuned click approach.