Julia Morales Sanfrutos

Centro Nacional de Investigaciones Oncológicas | CNIO · Biotechnology Programme, Proteomics Unit

Colorectal cancer (CRC) is among the most deadly cancers worldwide. Current therapeutic strategies have low success rates and several side effects. This relevant clinical problem requires the discovery of new and more effective therapeutic alternatives. Ruthenium drugs have arisen as one of the most promising metallodrugs, due to their high selecti...

Plant roots can exploit beneficial associations with soil inhabiting microbes, promoting growth and expanding the immune capacity of the host plant. In this work, we aimed to increase information on changes occurring in tomato interacting with the beneficial fungus Beauveria bassiana. Tomato leaf proteome revealed perturbed molecular pathways durin...

Introduction: The field of extracellular vesicles (EVs) is rapidly advancing. This progress is fuelled by the potential applications of these agents as biomarkers and also as an attractive source to encapsulate therapeutics and other agents to target specific cells. Areas covered: Different types of EVs, including exosomes, and other nanoparticl...

Over 170 post-transcriptional RNA modifications have been described and are common in all kingdoms of life. These modifications range from methylation to complex chemical structures, with methylation being the most abundant. RNA modifications play a key role in RNA folding and function and their dysregulation in humans has been linked to several di...

We have combined chemical biology and genetic modification approaches to investigate the importance of protein myristoylation in the human malaria parasite, Plasmodium falciparum . Parasite treatment during schizogony in the last 10 to 15 hours of the erythrocytic cycle with IMP-1002, an inhibitor of N -myristoyl transferase (NMT), led to a signifi...

Protein lipidation is one of the most widespread post-translational modifications (PTMs) found in nature, regulating protein function, structure and subcellular localization. Lipid transferases and their substrate proteins are also attracting increasing interest as drug targets because of their dysregulation in many disease states. However, the inh...

QCloud is a cloud-based system to support proteomics laboratories in daily quality assessment using a user-friendly interface, easy setup, and automated data processing. Since its release, QCloud has facilitated automated quality control for proteomics experiments in many laboratories. QCloud provides a quick and effortless evaluation of instrument...

We have combined chemical biology and genetic modification approaches to investigate the importance of protein myristoylation in the human malaria parasite, Plasmodium falciparum . Parasite treatment during schizogony in the last ten to fifteen hours of the erythrocytic cycle with IMP-1002, an inhibitor of N -myristoyl transferase (NMT), led to a s...

Sirtuins are key players of metabolic stress response. Originally described as deacetylases, some sirtuins also exhibit poorly understood mono–adenosine 5′-diphosphate (ADP)–ribosyltransferase (mADPRT) activity. We report that the deacetylase SirT7 is a dual sirtuin, as it also features auto-mADPRT activity. SirT7 mADPRT occurs at a previously unde...

Sirtuins are key players in the response to oxidative, metabolic and genotoxic stress, and are involved in genome stability, metabolic homeostasis and aging. Originally described as NAD+-dependent deacetylases, some sirtuins are also characterized by a poorly understood mono-ADP-ribosyltransferase (mADPRT) activity. Here we report that the deacetyl...

Post-translational farnesylation or geranylgeranylation at a C-terminal cysteine residue regulates the localization and function of over 100 proteins, including the Ras isoforms, and is a therapeutic target in diseases including cancer and infection. Here, we report global and selective profiling of prenylated proteins in living cells enabled by th...

N-myristoylation is the covalent addition of a 14-carbon saturated fatty acid (myristate) to the N-terminal glycine of specific protein substrates by N-myristoyltransferase (NMT) and plays an important role in protein regulation by controlling localization, stability, and interactions. We developed a novel method for whole-proteome profiling of fre...

Rhinoviruses (RVs) are the pathogens most often responsible for the common cold, and are a frequent cause of exacerbations in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Here we report the discovery of IMP-1088, a picomolar dual inhibitor of the human N-myristoyltransferases NMT1 and NMT2, and use it to demonstrate that pharm...

Diaminoquinazolines represent a privileged scaffold for antimalarial discovery, including use as putative Plasmodium histone lysine methyltransferase inhibitors. Despite this, robust evidence for their molecular targets is lacking. Here we report the design and development of a small-molecule photo-crosslinkable probe to investigate the targets of...

Starch binding domain-containing protein (Stbd)-1 is a carbohydrate-binding protein, which has been proposed as a selective autophagy receptor for glycogen. Here, we show that mouse Stbd1 is a transmembrane, endoplasmic reticulum (ER)-resident protein with the capacity to induce the formation of organized ER structures in HeLa cells. In addition to...

N-Myristoyltransferase (NMT) covalently attaches a C14 fatty acid to the N-terminal glycine of proteins and has been proposed as a therapeutic target in cancer. We have recently shown that selective NMT inhibition leads to dose-responsive loss of N-myristoylation on more than 100 protein targets in cells, and cytotoxicity in cancer cells. N-myristo...

The aim of this study was to evaluate the crosslinking abilities of divinyl sulfone (DVS) for the preparation of novel water-insoluble cyclodextrin-based polymers (CDPs) capable of forming inclusion complexes with different guest molecules. Reaction of DVS with native α-cyclodextrin (α-CD), β-cyclodextrin (β-CD) and/or starch generates a variety of...

Monoclonal antibodies have long in vivo half-lives and reach high concentrations in tumors but cannot access all regions in the tissue, whereas smaller ligands such as peptides distribute better but are limited by low concentrations due to fast renal clearance. A potential solution to this problem might be offered by peptide-based ligands that are...

Cyclodextrins have been conjugated to target various receptors and have also been functionalized with carbohydrates for targeting specific organs. However, this approach is based on a rigid design that implies the ad hoc synthesis of each cyclodextrin-targeting agent conjugate. We hypothesized that: 1) a modular design that decouples the carrier fu...

Bicyclic peptide ligands were found to have good binding affinity and target specificity. However, the method applied to generate bicyclic ligands based on phage-peptide alkylation is technically complex and limits its application to specialized laboratories. Herein, we report a method that involves a simpler and more robust procedure that addition...

La presente invención se refiere a compuestos poliméricos con propiedades inmovilizantes sobre biomoléculas. Dichos materiales comprenden un núcleo de nanopartículas híbridas súper-paramagnéticas y grupos vinilsulfona para llevar a cabo la inmovilización de las biomoléculas. Además la presente invención se refiere a un procedimiento de síntesis de...

Immunostimulating complexes (ISCOM)-type nanocapsules have been functionalized with lipid vinyl sulfones that anchor to them via the hydrophobic zone of their structure and can be charged with pharmacologically active molecules or macromolecules. These functionalized nanocapsules can incorporate protein A and bind to G immunoglobulins (IgGs) to mak...

13C and DEPT NMR spectra for compound 7.

1H NMR spectra for compound 9.

13C and DEPT NMR spectra for compound 9.

1H NMR spectra for compound 4.

13C and DEPT NMR spectra for compound 4.

1H NMR spectra for compound 7.

An electrochemiluminescent cholesterol disposable biosensor has been prepared by the formation of assembled layers on gold screen-printed cells. The detection layer is based on the electro-formation of new luminol copolymers with different synthesized biotinylated pyrroles prepared by click-chemistry, offering a new transduction layer with new elec...

Proteolytically stable peptide architectures are required for the development of long-acting peptide therapeutics. In this work, we found that a phage-selected bicyclic peptide antagonist exhibits an unusually high stability in vivo and subsequently deciphered the underlying mechanisms of peptide stabilization. We found that the bicyclic peptide wa...

The immobilization of biomols. on magnetic nanoparticles is an issue with high potential in different fields. We describe herein a new strategy to immobilize biomols. on super-paramagnetic nanoparticles based on the reactivity of vinyl sulfone groups with naturally occurring functional groups present in biomols. (amine and thiol). A new monomer con...

To extend the plasma half-life of a bicyclic peptide antagonist, we chose to link it to the Fc fragment of the long-lived serum protein IgG1. Instead of chemically conjugating the entire bicyclic peptide, we recombinantly expressed its peptide moiety as a fusion protein to an Fc fragment and subsequently cyclized the peptide by chemically reacting...

Combinatorial libraries of structurally diverse peptide macrocycles offer a rich source for the development of high-affinity ligands to targets of interest. In this work we have developed linkers for the generation of genetically encoded bicyclic peptides and tested whether the peptides cyclised by them have significant variations in their backbone...

Cyclic sulfites, sulfates and sulfamidates derived from saccharides have emerged as valuable and versatile synthons for the preparation of a wide variety of modified sugars and sugar related compounds owing to the combination of the easily and efficient formation of these chemical sulfur derivatives from diols and aminoalcohols with the high chemic...

Amphiphilic dendrimer-based gene delivery vectors bearing peripheral alkyl sulfonyl hydrophobic tails were constructed using low-generation PAMAM-G2 as the core and functionalized by means of the aza-Michael type addition of its primary amino groups to vinylsulfone derivatives as an efficient tool for surface engineering. While the unmodified PAMAM...

The combination of silica as support and vinyl sulfone as reactive group led to a pre-activated material that readily reacts to form covalent bonds by Michael-type addition with both amine and thiol groups naturally occurring in biomolecules in mild conditions compatible with the biological nature of the enzymes. A simple two step synthetic strateg...

The introduction of multiple labels onto biomolecules is a challenge. We report herein the synthesis of vinyl sulfone derivatized bifunctional tag single-attachment-point reagents (BTSAP) bearing biotin and a fluorescent tag and their applications in proteins for the introduction of multiple labels by means of the Michael-type addition of the elect...

The easy functionalization of tags and solid supports with the vinyl sulfone function is a valuable tool in omic sciences that allows their coupling with the amine and thiol groups present in the proteogenic residues of proteins, in mild and green conditions compatible with their biological function.

WO 2009/144344 A2 Compds. for labeling biomols. based on vinyl sulfone of formula I, their prepn. and uses, is disclosed. In addn. the invention relates to the use of compds. of formula I as labeling agents and uses thereof in marking biomols. and, more specifically, proteins. Compds. of formula I wherein X is O, S and (un)substituted C1-10 alkyl,...

WO 2009/106665 A1 The invention relates to labeling agents contg. a compd. with two labeled mols. and a vinyl sulfone group of formula I. The invention also relates to the compds. of formula I, the method for obtaining same and the uses thereof in the marking of biomols. and, more specifically, proteins. Compds. of formula I wherein L and L1 are in...

The efficient synthesis of structurally diverse, multivalent, heterogeneous neoglycoconjugates by means of a series of different click-based strategies is described. The methodology is highly efficient and versatile allowing for easy access to a series of mannose (α-Man)-containing glycoconjugates differing in their valency, nature of the scaffold,...

Mannose (α-Man)-containing neoglycoconjugates possessing aliphatic-, aromatic-, and carbohydrate-centered architectures and differing in structural characteristics such as valency, topology, and nature of the linker have been synthesized using click chemistry that shows its value as an efficient and versatile methodology for accessing tailor-made m...

The cover picture shows two copper(I) click-based strategies for accessing multivalent neoglyconjugates by the coupling of complementary functionalized scaffolds and sugar derivatives. The methodology allows the easy preparation of structurally diverse homogeneous neoglycoconjugates from which the influence of the structural parameters in the bindi...

WO 2009/040460 A1 Compd. which comprises a medium of silica functionalized with vinylsulfone groups. The functional group has the following structure: silica-Si-(CH2)n-X[R1]-CH2CH2-Y-SO2-CH=CH2, where X=S or N; R1 = alkyl group from C1-C10 substituted or not, or an alkenyl group (C1-C10) substituted or not; Y = SO2R2 or it may not be there. In addn...

We have covalently coupled fluorophore 4-(2-hydroxyethoxy)-7-nitro-2,1,3-benzoxadiazole (NBD) to the external ferritin shell through lysine residues. An increase in the luminescence quantum yield of the fluorescent ferritin particles and a blue shift in its emission peak compared to individual fluorophore were obsd. The study of the particles by tr...

The covalent synthesis of nanosized cage compounds is easily performed in high yields using "click chemistry" methodology through the Cu(I)-catalyzed ligation of adequate polyalkyne and polyazide derivatives using (EtO)3P x CuI as catalyst.

The synthesis of a variety of calixarene-based cavitands (capped and functional calixarenes) and calix nanotubes is easily performed in good to high yields using "click chemistry" methodology through the Cu(I)-catalyzed ligation of adequate bis-alkyne and bis-azide derivatives.

We report a flexible route to chemically modify the ferritin nanomagnet. Two dye-labeled ferritins (red- and blue-ferritin) have been prepared by covalently coupling the derivatives of the reactive orange 16 and Remazol brilliant blue R, respectively, to the ferritin surface lysine residues. The study of the particles by transmission electron micro...

The efficient synthesis of fluorescent and non-fluorescent multivalent neoglycoconjugates is described by means of the Cu(i) catalyzed azide-alkyne 1,3-dipolar cycloaddition ("click-chemistry"). A well-defined glycopolymer, glycocyclodextrin or glycocluster architecture displaying galactose or lactose epitopes has been chosen. Cellular assays using...

[reaction: see text] The construction of multivalent neoglycoconjugates is efficiently achieved by the regiospecific catalytic cycloaddition of alkynes and azides using the organic-soluble copper complexes (Ph(3)P)(3).CuBr and (EtO)(3)P.CuI. The simultaneous use of microwave irradiation shortened notably the reaction times.

Número de publicación: 2 319 063, Número de solicitud: 200702542 Compuesto de sílica-vinilsulfona, síntesis y usos del mismo. Compuesto que comprende un soporte de silica funcionalizada con grupos vinilsulfona. Además, se refiere a su procedimiento de obtención y sus usos como inmovilizador de biomoléculas, y más concretamente de enzimas tales como...