A5073771191- Protein Structure and Dynamics
- Chemical Synthesis and Analysis
- Cancer therapeutics and mechanisms
- HIV/AIDS drug development and treatment
- Cellular transport and secretion
- Enzyme Structure and Function
- DNA and Nucleic Acid Chemistry
- Advanced Chemical Physics Studies
- Biochemical and Molecular Research
- Spectroscopy and Laser Applications
- Lipid Membrane Structure and Behavior
- Peptidase Inhibition and Analysis
- Microtubule and mitosis dynamics
- HIV Research and Treatment
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- Adenosine and Purinergic Signaling
- Click Chemistry and Applications
- Molecular Spectroscopy and Structure
- Cyclization and Aryne Chemistry
- Genomics, phytochemicals, and oxidative stress
- Boron and Carbon Nanomaterials Research
- Nuclear Structure and Function
Instituto de Química Médica
2022
Universidad de Alcalá
2019-2021
Birkbeck, University of London
1991-1992
The University of Sydney
1930-1931
New multi-target indole and naphthalene derivatives containing the oxadiazolone scaffold as a bioisostere of melatonin acetamido group have been developed. The novel compounds were characterized at receptors MT1R MT2R, quinone reductase 2 (QR2), lipoxygenase-5 (LOX-5), monoamine oxidases (MAO-A MAO-B), also radical scavengers. We found that selectivity within series can be modulated by modifying side chain functionality co-planarity with or ring. In phenotypic assays, several...
Non-vesicular lipid transfer at ER and plasma membrane (PM) contact sites (CS) is crucial for the maintenance of homeostasis. Extended synaptotagmins (E-Syts) play a central role in this process as they act molecular tethers PM proteins between these organelles. E-Syts are constitutively anchored to through an N-terminal hydrophobic segment bind via variable number C-terminal C2 domains. Synaptotagmins (SYTs) plant orthologous regulate ER–PM communication response abiotic stress. Combining...
Abstract Unprecedented 3D hexa‐adducts of [60]fullerene peripherally decorated with twelve tryptophan (Trp) or tyrosine (Tyr) residues have been synthesized. Studies on the antiviral activity these novel compounds against HIV and EV71 reveal that they are much more potent equally active than previously described dendrimer prototypes AL‐385 AL‐463 , which possess same number Trp/Tyr periphery but attached to a smaller flexible pentaerythritol core. These results demonstrate relevance globular...
It is to be expected that the alkyl halides will dissociate on absorption of light into residues and excited halogen atoms. Their spectra are continuous, as also case with phenyl iodide, which liberates iodine under identical conditions. The C-I C-Br linkages certainly homopolar in gas state. On Franck’s theory long-wave limit continuum should correspond heat binding together excitation energy atom. We would expect resemble hydrides their behaviour, although HI HBr limits not very happily...
Abstract Pyruvate dehydrogenase complex (PDC) deficiency caused by mutations in the X-linked PDHA1 gene has a broad clinical presentation, and pattern of X-chromosome inactivation been proposed as major factor contributing to its variable expressivity heterozygous females. Here, we report first set monozygotic twin females with PDC deficiency, novel, de novo missense mutation exon 11 (NM_000284.3: c.1100A>T). Both twins presented infancy similar phenotype including developmental delay,...
Abstract The use of nucleoside 2′‐deoxyribosyltransferases (NDTs) as biocatalysts for the industrial synthesis analogues is often hindered by their strict preference 2′‐deoxyribonucleosides. It shown herein that a highly versatile purine NDT from Trypanosoma brucei ( Tb PDT) can also accept ribonucleosides substrates; this most likely because distinct role played Asn53 at position usually occupied Asp in other NDTs. Moreover, unusual activity was improved about threefold introducing single...
We have recently described a new generation of potent human immunodeficiency virus (HIV) and EV-A71 entry inhibitors. The prototypes contain three or four tryptophan (Trp) residues bearing an isophthalic acid moiety at the C2 position each side-chain indole ring. This work is now extended by both shifting to C7 synthesizing doubly arylated C2/C7 derivatives. most derivative (50% effective concentration (EC50) HIV-1, 6 nM; EC50 EV-A71, 40 nM), 33 (AL-518), tetrapodal compound. Its superior...
Abstract Spontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post‐translationally modified dimer that provides information about sites interaction with numerous binding partners, including itself, maps these onto tetramer interfaces. spatial locations side chain carboxylates Glu301 Glu374, to which phosphatidylethanolamine is uniquely attached via an amide...
Atomistic molecular dynamics simulations shed structural light on the curvature inflicted DNA upon binding of calicheamicin ε to high-affinity and low-affinity target sites.
We have recently described a novel family of compounds reduced size and dual anti-HIV anti-EV71 activity that encompasses tripodal tetrapodal derivatives. The prototype, AL-470, has nitro group at the focal point central scaffold three attached tryptophan residues, each which bearing an isophthaloyl moiety C2 position indole ring. A to amino substitution allowed us now introduce chemically addressable functionality perform further structural modifications consisting both direct...
Foot-and-mouth disease virus (FMDV) is an RNA belonging to the Picornaviridae family that contains three small viral proteins (VPgs), named VPg1, VPg2 and VPg3, linked 5'-end of genome. These VPg act as primers for replication, which initiated by consecutive binding two UMP molecules hydroxyl group Tyr3 in VPg. This process, termed uridylylation, catalyzed RNA-dependent polymerase 3Dpol. 5-Fluorouridine triphosphate (FUTP) a potent competitive inhibitor uridylylation. Peptide analysis showed...
A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive P-glycoprotein βIII-tubulin overexpressed drug-resistant cancer cell lines evaluated. It is demonstrated that C-seco conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on tumors overexpressing both βIII P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group...
The experimental construction of a double-stranded DNA microcircle only 42 base pairs entailed great deal ingenuity and hard work. However, figuring out the three-dimensional structures intermediates final product can be particularly baffling. Using combination model building unrestrained molecular dynamics simulations in explicit solvent we have characterized different involved along process. Our 3D models single-stranded molecules provide atomic insight into recognition event that must...
Abstract Cell function requires the maintenance of membrane lipid homeostasis as changes in cellular environment unbalance this equilibrium. The non-vesicular transfer at endoplasmic reticulum (ER) and plasma (PM) contact sites (CS) is central to restore it. Extended synaptotagmins (E-Syts) are ER proteins that play a role process they act molecular tethers with PM between these organelles. E-Syts constitutively anchored through an N-terminal hydrophobic segment bind via C-terminal C2...