A5009977581- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- HER2/EGFR in Cancer Research
- Click Chemistry and Applications
- Lung Cancer Treatments and Mutations
- Antibiotic Resistance in Bacteria
- Antimicrobial Peptides and Activities
- Photochromic and Fluorescence Chemistry
- Sleep and Wakefulness Research
- Cancer Immunotherapy and Biomarkers
- Biochemical and Structural Characterization
- Circadian rhythm and melatonin
- Neuropeptides and Animal Physiology
- Parkinson's Disease Mechanisms and Treatments
- Bacterial biofilms and quorum sensing
- Eicosanoids and Hypertension Pharmacology
- Venomous Animal Envenomation and Studies
- Lipid Membrane Structure and Behavior
- Toxin Mechanisms and Immunotoxins
- Hormonal Regulation and Hypertension
- Computational Drug Discovery Methods
- Cancer Genomics and Diagnostics
- Renin-Angiotensin System Studies
Institute for Research in Biomedicine
2015-2024
Institute of Science and Technology
2021
Barcelona Institute for Science and Technology
2017-2021
Shanghai Institute for Science of Science
2018-2021
FC Barcelona
2018-2021
Institute for Research in Biomedicine
2019
Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, process that current therapeutic approaches cannot prevent. In PD, the typical pathological hallmark accumulation intracellular protein inclusions, known as Lewy bodies and neurites, which are mainly composed α-synuclein. Here, we exploited high-throughput screening methodology to identify small molecule (SynuClean-D) able inhibit α-synuclein aggregation. SynuClean-D significantly reduces in vitro...
Preventing the adhesion of pathogens to host cells provides an innovative approach tackling multidrug-resistant bacteria. In this regard, identification outer membrane protein A (OmpA) as a key bacterial virulence factor has been major breakthrough. The use virtual screening helped us identify cyclic hexapeptide AOA-2 that inhibits Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli formation biofilm, thereby preventing development infection in vitro murine sepsis peritoneal...
Prolyl oligopeptidase (POP), a serine protease highly expressed in the brain, has recently emerged as an enticing therapeutic target for treatment of cognitive and neurodegenerative disorders. However, most reported inhibitors suffer from short duration action, poor selectivity, low blood-brain barrier (BBB) permeability, which altogether limit their potential drugs. Here, we describe structure-based design first irreversible, selective, brain-permeable POP inhibitors. At low-nanomolar...
Peptides are a rapidly growing class of therapeutics with various advantages over traditional small molecules, especially for targeting difficult protein-protein interactions. However, current structure-based methods largely limited to natural peptides and not suitable designing bioactive cyclic topologies that go beyond l-amino acids. Here, we report generalizable framework exploits the computational power Rosetta, in terms large-scale backbone sampling, side-chain composition energy...
Epidermal growth factor receptor (EGFR) is a key target in chemotherapy. Some drugs acting on the are currently use; however, drug resistance, which causes tumour relapse, calls for discovery of alternative inhibitors. Using docking and hotspot mimicry, we have designed novel peptides directed at EGF, main ligand EGFR. An array biophysical techniques was used to characterise structure interaction these ligands with protein. Both design methods identified able bind capacity inhibit between...
Abstract In cancer, proliferation of malignant cells is driven by overactivation growth‐signalling mechanisms, such as the epidermal growth factor receptor (EGFR) pathway. Despite its therapeutic relevance, EGF–EGFR interaction has remained elusive to inhibition synthetic molecules, mostly a result large size and lack binding pockets cavities. Designed peptides, featuring cyclic motifs other structural constraints, have potential modulate challenging protein–protein interactions (PPIs)....
The present study aims to develop chlorotoxin (CTX), from Giant Yellow Israeli scorpion venom, as a new BBB-shuttle. Minimised versions of CTX were prepared reduce its complexity while enhancing BBB-shuttle capacity and preserving protease-resistance. MiniCTX3, monocyclic lactam-bridge peptidomimetic, was capable transporting nanoparticles across endothelial cell monolayers. Our results reveal animal venoms an outstanding source families BBB-shuttles.
Abstract One of the hallmarks cancer is overproduction growth factors such as EGF. Despite clinical success achieved by EGFR‐targeted therapies, their long‐term efficacy compromised onset drug‐resistant mutations. To address this issue, a family camelid‐derived single‐domain antibodies (Nbs) were generated, obtaining first direct EGF inhibitors that prevent EGFR phosphorylation and pathway activation through new mechanism action. The two best Nbs subjected to detailed investigation...
The epidermal growth factor (EGF) pathway, being overactive in a number of cancers, is good target for clinical therapy. Although several drugs targeting the EGF receptor (EGFR) are on market, tumours acquire resistance very rapidly. As an alternative, small molecules and peptides have been developed, although with moderate success. Herein, we report use mirror-image phage display technology to discover protease-resistant capacity inhibit EGF-EGFR interaction. After chemical synthesis...
Abstract Objectives Protegrins are a family of natural peptides from the innate immune system vertebrates, with broad-spectrum antimicrobial activity. However, toxicity and haemolysis protegrin-1 (PG-1) at low concentrations renders it useless for therapeutic application. We rationally designed PLP-3, novel synthetic PG-1-like peptide, comprising key activity features protegrins in constrained bicyclic structure. Our main objective was to investigate PLP-3’s against MDR strains Acinetobacter...
Despite the widespread use of antibodies in clinical applications, precise molecular mechanisms underlying antibody–antigen (Ab–Ag) interactions are often poorly understood. In this study, we exploit technical features a typical surface plasmon resonance (SPR) biosensor to dissect kinetic and thermodynamic components that govern binding single-domain Ab or nanobodies their target antigen, epidermal growth factor (EGF), key oncogenic protein is involved tumour progression. By carefully tuning...
Abstract One of the hallmarks cancer is overproduction growth factors such as EGF. Despite clinical success achieved by EGFR‐targeted therapies, their long‐term efficacy compromised onset drug‐resistant mutations. To address this issue, a family camelid‐derived single‐domain antibodies (Nbs) were generated, obtaining first direct EGF inhibitors that prevent EGFR phosphorylation and pathway activation through new mechanism action. The two best Nbs subjected to detailed investigation...
Abstract We report a quantitative proteomics data analysis pipeline, which coupled to protein‐directed dynamic combinatorial chemistry (DDC) experiments, enables the rapid discovery and direct characterization of protein‐protein interaction (PPI) modulators. A low‐affinity PD‐1 binder was incubated with library >100 D‐peptides under thiol‐exchange favoring conditions, in presence target protein PD‐1, we determined S‐linked dimeric species that resulted, amplified samples versus controls....
Orexinergic neurons are critically involved in regulating arousal, wakefulness, and appetite. Their dysfunction has been associated with sleeping disorders, non-peptide drugs currently being developed to treat insomnia narcolepsy. Yet, no light-regulated agents available reversibly control their activity. To meet this need, a photoswitchable peptide analogue of the endogenous neuroexcitatory orexin-B was designed, synthesized, tested vitro vivo. This compound - photorexin is first...
Orexinergic neurons are critically involved in regulating arousal, wakefulness, and appetite. Their dysfunction has been associated with sleeping disorders, non-peptide drugs currently being developed to treat insomnia narcolepsy. Yet, no light-regulated agents available reversibly control their activity. To meet this need, a photoswitchable peptide analogue of the endogenous neuroexcitatory orexin-B was designed, synthesized, tested vitro vivo. This compound (photorexin) is first...
EGFR, the receptor for epidermal growth factor (EGF), is arguably considered most important therapeutic target in contemporary anticancer treatments. However, 20 years after introduction of anti-EGFR drugs into clinical setting, a number severe drawbacks have been observed, namely low tumour penetration monoclonal antibodies, acquisition resistance to tyrosine-kinase inhibitors, and complete lack efficacy several types cancer. Here, we report design strategy obtain all-D peptides directed...
Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods largely limited natural peptides and not suitable for designing target-specific binders improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages computational power of Rosetta large-scale backbone sampling energy scoring, followed by side-chain composition,...
The reaction of a series 1,2-diols with thionyl chloride led to bisnoradamantane sulfites in very good yields. has also been applied related polycyclic scaffolds. compounds have tested for antiviral activity but none them showed be active. Several attempts generate and trap SO from these unsuccessful. Keywords: Antiviral activity, bisnoradamantanes, compounds, sulfites, sulfur monoxide, vesicular stomatitis virus, 1,2-diols, chloride, adamantane, ring-contracted analogs, memantine, rimantadine