A5040206260- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Supramolecular Self-Assembly in Materials
- Click Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- Innovative Microfluidic and Catalytic Techniques Innovation
- Biochemical and Structural Characterization
- S100 Proteins and Annexins
- Peptidase Inhibition and Analysis
- Nanoparticle-Based Drug Delivery
- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Blood Coagulation and Thrombosis Mechanisms
- Venomous Animal Envenomation and Studies
- Microbial Natural Products and Biosynthesis
- Bacteriophages and microbial interactions
- Ion channel regulation and function
- RNA Interference and Gene Delivery
- Tuberculosis Research and Epidemiology
- Protein purification and stability
- ATP Synthase and ATPases Research
- Nanofabrication and Lithography Techniques
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- CAR-T cell therapy research
École Polytechnique Fédérale de Lausanne
2020-2023
Institut Químic de Sarrià
2023
Universitat Ramon Llull
2023
Institute for Research in Biomedicine
2016-2019
Institute for Research in Biomedicine
2019
Barcelona Institute for Science and Technology
2018
Shanghai Institute for Science of Science
2018
FC Barcelona
2018
THRre is a protease resistant BBB-shuttle. A branched version of displaying two copies the peptide increases transport model protein in BBB cell-based models.
Abstract Macrocycles have excellent potential as therapeutics due to their ability bind challenging targets. However, generating macrocycles against new targets is hindered by a lack of large macrocycle libraries for high-throughput screening. To overcome this, we herein established combinatorial approach tethering myriad chemical fragments peripheral groups structurally diverse macrocyclic scaffolds in fashion, all at picomole scale nanoliter volumes using acoustic droplet ejection...
The widespread expression of many therapeutic targets in both diseased and healthy tissues presents a significant challenge for protein therapeutics, often resulting dose-limiting side effects. To focus the action biotherapeutics at disease site, they can be reversibly inactivated by tethering an affinity mask through linker cleavable disease-specific cue. However, current methods to generate masks require extensive screening masking sequence libraries. Here, we report workflow design first...
Most potential drugs for the treatment of central nervous system disorders do not cross blood-brain barrier (BBB). Much research effort has been devoted to discovery new BBB-shuttle peptides-most which have identified by phage display. Here we report first time on use display against a human BBB cellular model mimics characteristics BBB. From panning experiment 12-mer library, SGVYKVAYDWQH (SGV) peptide sequence was selected and its permeability validated in aforementioned model....
Abstract Common inflammatory disorders such as ulcerative colitis and Crohn’s disease are non-invasively diagnosed or monitored by the biomarker calprotectin. However, current quantitative tests for calprotectin antibody-based vary depending on type of antibody assay used. Additionally, binding epitopes applied antibodies not characterized structures most it is unclear if they detect dimer, tetramer, both. Herein, we develop ligands based peptides, that offer advantages homogenous chemical...
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.
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...
The success of phage display, used for developing target-specific binders based on peptides and proteins, depends the size diversity library screened, but generating large libraries phage-encoded polypeptides remains challenging. New peptide display developed in recent years rarely contained more than 1 billion clones, which appears to have become upper limit generated with reasonable effort. Here, we established a strategy whole-plasmid PCR self-ligation clone 2 × 1010 members. enormous...
Macrocyclic compounds are an attractive class of therapeutic ligands against challenging targets, such as protein-protein interactions. However, the development macrocycles drugs is hindered by lack large combinatorial macrocyclic libraries, which cumbersome, expensive, and time consuming to make, screen, deconvolute. Here, we established a strategy for synthesizing screening libraries on picomolar scale using acoustic droplet ejection combine building blocks at nanoliter volumes, reduced...
Phage display is a powerful technique routinely used for the generation of peptide- or protein-based ligands. The success phage selections critically depends on size and structural diversity libraries, but large libraries remains challenging. In this work, we have succeeded in developing library comprising around 100 billion different (bi)cyclic peptides thus more structures than any previously reported cyclic peptide library. Building such high was achieved by combining recently cloning...
BrainBikes, a new family of bicyclic brain shuttle peptides, can efficiently transport protein therapeutics across endothelium.
Coagulation factor XI (FXI) has emerged as a promising target for the development of safer anticoagulation drugs that limit risk severe and life-threatening bleeding. Herein, we report first cyclic peptide-based FXI inhibitor selectively potently inhibits activated (FXIa) in human animal blood. The peptide (Ki = 2.8 ± 0.5 nM) achieved effects are comparable to gold standard heparin applied at therapeutic dose (0.3–0.7 IU/mL plasma) but with substantially broader estimated range. We extended...
Antibody therapeutics show great potential to treat a variety of diseases. Often, the dose that can be safely administered is limited by side effects arise from interaction with target outside diseased tissue. Conditionally-active antibodies provide an additional layer selectivity improve safety. Distinct external stimuli or internal cues enable different control strategies and applications. However, current antibody masking have low transferability across stimuli. Here we propose versatile...
Abstract Macrocyclic compounds are an attractive class of therapeutic ligands against challenging targets, such as protein–protein interactions. However, the development macrocycles drugs is hindered by lack large combinatorial macrocyclic libraries, which cumbersome, expensive, and time consuming to make, screen, deconvolute. Here, we established a strategy for synthesizing screening libraries on picomolar scale using acoustic droplet ejection combine building blocks at nanoliter volumes,...
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...