Alcántara León, Andrés Rafael

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First Name
Andrés Rafael
Last Name
Alcántara León
Universidad Complutense de Madrid
Faculty / Institute
Química en Ciencias Farmacéuticas
Química Orgánica
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Now showing 1 - 10 of 12
  • Publication
    Genipin as An Emergent Tool in the Design of Biocatalysts: Mechanism of Reaction and Applications
    (MDPI, 2019-12-06) Tacias-Pascacio, Veymar G.; García-Parra, Esmeralda; Vela-Gutiérrez, Gilber; Virgen-Ortiz, Jose J.; Berenguer-Murcia, Ángel; Alcántara León, Andrés Rafael; Fernandez-Lafuente, Roberto
    Genipin is a reagent isolated from the Gardenia jasminoides fruit extract, and whose low toxicity and good crosslinking properties have converted it into a reactive whose popularity is increasing by the day. These properties have made it widely used in many medical applications, mainly in the production of chitosan materials (crosslinked by this reactive), biological scaffolds for tissue engineering, and nanoparticles of chitosan and nanogels of proteins for controlled drug delivery, the genipin crosslinking being a key point to strengthen the stability of these materials. This review is focused on the mechanism of reaction of this reagent and its use in the design of biocatalysts, where genipin plays a double role, as a support activating agent and as inter- or intramolecular crosslinker. Its low toxicity makes this compound an ideal alterative to glutaraldehyde in these processes. Moreover, in some cases the features of the biocatalysts prepared using genipin surpassed those of the biocatalysts prepared using other standard crosslinkers, even disregarding toxicity. In this way, genipin is a very promising reagent in the design of biocatalysts.
  • Publication
    One Pot Use of Combilipases for Full Modification of Oils and Fats: Multifunctional and Heterogeneous Substrates
    (MDPI, 2020-05-29) Arana-Peña, Sara; Carballares, Diego; Berenguer-Murcia, Ángel; Alcántara León, Andrés Rafael; Rodrigues, Rafael; Fernandez-Lafuente, Roberto
    Lipases are among the most utilized enzymes in biocatalysis. In many instances, the main reason for their use is their high specificity or selectivity. However, when full modification of a multifunctional and heterogeneous substrate is pursued, enzyme selectivity and specificity become a problem. This is the case of hydrolysis of oils and fats to produce free fatty acids or their alcoholysis to produce biodiesel, which can be considered cascade reactions. In these cases, to the original heterogeneity of the substrate, the presence of intermediate products, such as diglycerides or monoglycerides, can be an additional drawback. Using these heterogeneous substrates, enzyme specificity can promote that some substrates (initial substrates or intermediate products) may not be recognized as such (in the worst case scenario they may be acting as inhibitors) by the enzyme, causing yields and reaction rates to drop. To solve this situation, a mixture of lipases with different specificity, selectivity and differently affected by the reaction conditions can offer much better results than the use of a single lipase exhibiting a very high initial activity or even the best global reaction course. This mixture of lipases from different sources has been called “combilipases” and is becoming increasingly popular. They include the use of liquid lipase formulations or immobilized lipases. In some instances, the lipases have been coimmobilized. Some discussion is offered regarding the problems that this coimmobilization may give rise to, and some strategies to solve some of these problems are proposed. The use of combilipases in the future may be extended to other processes and enzymes.
  • Publication
    Biocatalysis as Useful Tool in Asymmetric Synthesis: An Assessment of Recently Granted Patents (2014–2019)
    (MDPI, 2019-09-25) María, Pablo de; Gonzalo, Gonzalo de; Alcántara León, Andrés Rafael
    The broad interdisciplinary nature of biocatalysis fosters innovation, as different technical fields are interconnected and synergized. A way to depict that innovation is by conducting a survey on patent activities. This paper analyses the intellectual property activities of the last five years (2014–2019) with a specific focus on biocatalysis applied to asymmetric synthesis. Furthermore, to reflect the inventive and innovative steps, only patents that were granted during that period are considered. Patent searches using several keywords (e.g., enzyme names) have been conducted by using several patent engine servers (e.g., Espacenet, SciFinder, Google Patents), with focus on granted patents during the period 2014–2019. Around 200 granted patents have been identified, covering all enzyme types. The inventive pattern focuses on the protection of novel protein sequences, as well as on new substrates. In some other cases, combined processes, multi-step enzymatic reactions, as well as process conditions are the innovative basis. Both industries and academic groups are active in patenting. As a conclusion of this survey, we can assert that biocatalysis is increasingly recognized as a useful tool for asymmetric synthesis and being considered as an innovative option to build IP and protect synthetic routes.
  • Publication
    Biocatalysis and Pharmaceuticals: A Smart Tool for Sustainable Development
    (MDPI, 2019-09-23) Alcántara León, Andrés Rafael
  • Publication
    Multienzymatic Processes Involving Baeyer–Villiger Monooxygenases
    (MDPI, 2021-05-08) Gonzalo, Gonzalo de; Alcántara León, Andrés Rafael
    Baeyer–Villiger monooxygenases (BVMOs) are flavin-dependent oxidative enzymes capable of catalyzing the insertion of an oxygen atom between a carbonylic Csp2 and the Csp3 at the alpha position, therefore transforming linear and cyclic ketones into esters and lactones. These enzymes are dependent on nicotinamides (NAD(P)H) for the flavin reduction and subsequent reaction with molecular oxygen. BVMOs can be included in cascade reactions, coupled to other redox enzymes, such as alcohol dehydrogenases (ADHs) or ene-reductases (EREDs), so that the direct conversion of alcohols or α,β-unsaturated carbonylic compounds to the corresponding esters can be achieved. In the present review, the different synthetic methodologies that have been performed by employing multienzymatic strategies with BVMOs combining whole cells or isolated enzymes, through sequential or parallel methods, are described, with the aim of highlighting the advantages of performing multienzymatic systems, and show the recent advances for overcoming the drawbacks of using BVMOs in these techniques.
  • Publication
    Dextran Aldehyde in Biocatalysis: More Than a Mere Immobilization System
    (MDPI, 2019-07-21) Tacias-Pascacio, Veymar G.; Ortiz, Claudia; Rueda, Nazzoly; Berenguer-Murcia, Ángel; Acosta Contreras, Niuris; Aranaz Corral, Inmaculada; Civera Tejuca, María Concepción; Fernandez-Lafuente, Roberto; Alcántara León, Andrés Rafael
    Dextran aldehyde (dexOx), resulting from the periodate oxidative cleavage of 1,2-diol moiety inside dextran, is a polymer that is very useful in many areas, including as a macromolecular carrier for drug delivery and other biomedical applications. In particular, it has been widely used for chemical engineering of enzymes, with the aim of designing better biocatalysts that possess improved catalytic properties, making them more stable and/or active for different catalytic reactions. This polymer possesses a very flexible hydrophilic structure, which becomes inert after chemical reduction; therefore, dexOx comes to be highly versatile in a biocatalyst design. This paper presents an overview of the multiple applications of dexOx in applied biocatalysis, e.g., to modulate the adsorption of biomolecules on carrier surfaces in affinity chromatography and biosensors design, to serve as a spacer arm between a ligand and the support in biomacromolecule immobilization procedures or to generate artificial microenvironments around the enzyme molecules or to stabilize multimeric enzymes by intersubunit crosslinking, among many other applications.
  • Publication
    Biocatalyzed synthesis of antidiabetic drugs: A review
    (Taylor & Francis, 2018-02) Alcántara, Cristina M.; Alcántara León, Andrés Rafael
    The biocatalyzed production of building blocks for synthesizing drugs is a very attractive research field, because of the sustainability introduced in a synthetic schedule when chemical steps are substituted by biocatalyzed protocols. In this article, we will show how different antidiabetic drugs, for treating diabetes mellitus Type 1 and Type 2, can be more efficiently and effectively synthetized with the help of different types of biocatalysts. The huge overall drug market for these drugs, as well as the great number of people suffering from diabetes (the prevalence of all types of diabetes is growing), makes this topic attractive enough to focus on more efficient synthetic protocols for preparing antidiabetic drugs. Examples covering biocatalyzed synthesis of insulin analogues, sensitizers (PPAR agonists), secretagogues (GLP-1 analogues, GPR119 agonists) and enzyme inhibitors (α-glucosidase inhibitors, DPP4-inhibitors, SGLT-2 inhibitors and 11β-HSD1 inhibitors) will be presented.
  • Publication
    Biocatalyzed Synthesis of Statins: A Sustainable Strategy for the Preparation of Valuable Drugs
    (MDPI, 2019-03-14) Hoyos Vidal, Pilar; Pace, Vittorio; Alcántara León, Andrés Rafael
    Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are the largest selling class of drugs prescribed for the pharmacological treatment of hypercholesterolemia and dyslipidaemia. Statins also possess other therapeutic effects, called pleiotropic, because the blockade of the conversion of HMG-CoA to (R)-mevalonate produces a concomitant inhibition of the biosynthesis of numerous isoprenoid metabolites (e.g., geranylgeranyl pyrophosphate (GGPP) or farnesyl pyrophosphate (FPP)). Thus, the prenylation of several cell signalling proteins (small GTPase family members: Ras, Rac, and Rho) is hampered, so that these molecular switches, controlling multiple pathways and cell functions (maintenance of cell shape, motility, factor secretion, differentiation, and proliferation) are regulated, leading to beneficial effects in cardiovascular health, regulation of the immune system, anti-inflammatory and immunosuppressive properties, prevention and treatment of sepsis, treatment of autoimmune diseases, osteoporosis, kidney and neurological disorders, or even in cancer therapy. Thus, there is a growing interest in developing more sustainable protocols for preparation of statins, and the introduction of biocatalyzed steps into the synthetic pathways is highly advantageous—synthetic routes are conducted under mild reaction conditions, at ambient temperature, and can use water as a reaction medium in many cases. Furthermore, their high selectivity avoids the need for functional group activation and protection/deprotection steps usually required in traditional organic synthesis. Therefore, biocatalysis provides shorter processes, produces less waste, and reduces manufacturing costs and environmental impact. In this review, we will comment on the pleiotropic effects of statins and will illustrate some biotransformations nowadays implemented for statin synthesis.
  • Publication
    Desarrollo de una aplicación informática para dispositivos móviles para la mejora del aprendizaje de la nomenclatura de compuestos orgánicos y de fármacos
    (2019-03-29) Giorgi, Giorgio; López-Alvarado Gutiérrez, María del Pilar; Sánchez Cebrián, Juan Domingo; Alcántara León, Andrés Rafael; Fernández Fernández, María; Söllhuber Kretzer, Mónica; Pedregal Freire, Carmen; Campo Pérez, Carmen del; Salazar Martínez de Pisón, María Loreto; Cledera Crespo, María del Pilar; Llorente Ramos, Jesús Manuel; Bravo Llatas, María del Carmen; Martín Cámara, Olmo; Hortelano Morales, Marta; Capacchione, Marcello
  • Publication
    Evaluación de TuFormulas. Diseño y aplicación de indicadores para medir el impacto y la sostenibilidad de este recurso educativo como herramienta de enseñanza y aprendizaje
    (2021-03-30) Giorgi Poletti, Giorgio; Söllhuber Kretzer, Mónica; Pedregal Freire, Carmen; Campo Pérez, Carmen Luisa del; Salazar Martínez de Pisón, María Loreto; Fernández Fernández, María; Alcántara León, Andrés Rafael; Torrecilla Velasco, José Santiago; Tijero Cruz, Antonio; Bravo Llatas, María del Carmen; Martín Cámara, Olmo; Muñoz Silva, Miguel; Hortelano Morales, Marta; Capacchione, Marcello; Farrán Morales, María de los Ángeles; Ballesteros Martín, María de la Menta; Moral Rama, Ana; Sandoval Barrantes, Manuel; Syedd Leon, Randall; Carballo Arce, Ana; Guevara, Vielka; Patiño Cano, Laura Patricia; Recabarren Gajardo, Gonzalo; Zaderenko Partida, Ana Paula