A5085745476- Click Chemistry and Applications
- Radiopharmaceutical Chemistry and Applications
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Advanced Proteomics Techniques and Applications
- Molecular Sensors and Ion Detection
- Bone health and treatments
- Nitric Oxide and Endothelin Effects
- Medical Imaging and Pathology Studies
- Epigenetics and DNA Methylation
- Cardiac Imaging and Diagnostics
- Medical Imaging Techniques and Applications
- Photochromic and Fluorescence Chemistry
- Protease and Inhibitor Mechanisms
- Sulfur Compounds in Biology
- Lipid Membrane Structure and Behavior
- Metal complexes synthesis and properties
- RNA Interference and Gene Delivery
- Venous Thromboembolism Diagnosis and Management
- Enzyme function and inhibition
- Radical Photochemical Reactions
- Electron Spin Resonance Studies
- Sulfur-Based Synthesis Techniques
- Cell Adhesion Molecules Research
University of Lisbon
2010-2023
University of Cambridge
2016-2021
Instituto de Medicina Molecular João Lobo Antunes
2018
Harvard University
2014-2017
Massachusetts General Hospital
2014-2017
Instituto Superior Técnico
2012-2017
Athinoula A. Martinos Center for Biomedical Imaging
2014-2017
University of Pennsylvania
2015
Institute for Learning Innovation
2015
Medical University of the Americas
2014
Site-selective chemical conjugation of synthetic molecules to proteins expands their functional and therapeutic capacity. Current protein modification methods, based on biochemical technologies, can achieve site selectivity, but these techniques often require extensive sequence engineering or are restricted the N- C-terminus. Here we show computer-assisted design sulfonyl acrylate reagents for a single lysine residue native sequences. This feature designed acrylates, together with innate...
Abstract Maleimides remain the reagents of choice for preparation therapeutic and imaging protein conjugates despite known instability resulting products that undergo thiol-exchange reactions in vivo . Here we present rational design carbonylacrylic chemoselective cysteine bioconjugation. These rapid thiol Michael-addition under biocompatible conditions stoichiometric amounts. When using equipped with PEG or fluorophore moieties, this method enables access to antibody precisely modified at...
Abstract The cleavage of a protecting group from protein or drug under bioorthogonal conditions enables accurate spatiotemporal control over activity. Disclosed herein is that vinyl ethers serve as groups for alcohol‐containing molecules and reagents bond‐cleavage reactions. A ether moiety was installed in range molecules, including amino acids, monosaccharide, fluorophore, an analogue the cytotoxic duocarmycin. Tetrazine‐mediated decaging proceeded biocompatible with good yields reasonable...
The ability to create ways control drug activation at specific tissues while sparing healthy remains a major challenge. administration of exogenous target-specific triggers offers the potential for traceless release active drugs on tumor sites from antibody–drug conjugates (ADCs) and caged prodrugs. We have developed metal-mediated bond-cleavage reaction that uses platinum complexes [K2PtCl4 or Cisplatin (CisPt)] activation. Key success is water-promoted process reactivity complexes. Under...
We describe the development of a bifunctional linker that simultaneously allows site-specific protein modification and palladium-mediated bioorthogonal decaging.
Abstract The detection of externalized phosphatidylserine (PS) on the cell surface is commonly used to distinguish between living, apoptotic, and necrotic cells. tools choice for many researchers study apoptosis are annexin V‐fluorophore conjugates. However, use this 35 kDa protein associated with several drawbacks, including temperature sensitivity, Ca 2+ dependence, slow binding kinetics. Herein, a fluorogenic probe PS, P‐IID , described, which operates by an intramolecular indicator...
The ability to control the activation of prodrugs by transition metals has been shown have great potential for controlled drug release in cancer cells. However, strategies developed so far promote cleavage C–O or C–N bonds, which limits scope drugs only those that present amino hydroxyl groups. Here, we report decaging an ortho-quinone prodrug, a propargylated β-lapachone derivative, through palladium-mediated C–C bond cleavage. reaction's kinetic and mechanistic behavior was studied under...
Fibrin is a major component of arterial and venous thrombi represents an ideal candidate for molecular imaging thrombosis. Here, we describe properties target uptake new fibrin-specific positron emission tomographic probe thrombus detection therapy monitoring in 2 rat thrombosis models.The fibrin-binding FBP7 was synthesized by conjugation known short cyclic peptide to cross-bridged chelator (CB-TE2A), followed labeling with copper-64. Adult male Wistar rats (n=26) underwent either carotid...
Thrombosis is a leading cause of morbidity and mortality worldwide. Current diagnostic strategies rely on imaging modalities that are specific for distinct vascular territories, but thrombus-specific whole-body approach still missing. Moreover, techniques to assess thrombus composition underdeveloped, although therapeutic may benefit from such technology. Therefore, our goal was test whether positron emission tomography (PET) with the fibrin-binding probe (64)Cu-FBP8 allows multisite...
Norbornene derivatives were validated as probes for cysteine sulfenic acid on proteins and in live cells. Trapping acids with norbornene is highly selective revealed a different reactivity profile than the traditional dimedone reagent. The probe also superior chemoselectivity when compared to commonly used probe. Together, these results advance study of oxidation biological systems.
Bone scintigraphy with 99mTechnetium-methylenediphosphonate (99mTc-MDP) or 99mTechnetium-hydroxymethylenediphosphonate (99mTc-HMDP) presents several limitations, namely low specificity, uncertainty in the radiopharmaceutical's molecular structure and long acquisition time after injection. Aiming to find bone-seeking radiotracers based on core fac-[99mTc(CO)3]+ improved chemical biological properties, we synthesized new conjugates (pz-PAM pz-ALN), comprising a pyrazolyl-diamine chelating unit...
Background: Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be inability therapeutics to penetrate into dense mineral, which can lead poor efficacy high toxicity, due drug uptake healthy organs. The development nanostructured formulations with affinity for could an interesting approach overcome these challenges. Purpose: To develop liposomal formulation hydroxyapatite ability...
Abstract The unstrained S‐allyl cysteine amino acid was site‐specifically installed on apoptosis protein biomarkers and further used as a chemical handle ligation partner for 1,2,4,5‐tetrazines by means of an inverse‐electron‐demand Diels–Alder reaction. We demonstrate the utility this minimal efficient labeling apoptotic cells using fluorogenic tetrazine dye in pre‐targeting approach. small size, easy installation, selective reactivity towards tetrazines should be readily extendable to...
Thrombus formation plays a major role in cardiovascular diseases, but noninvasive thrombus imaging is still challenging. Fibrin component of both arterial and venous thrombi represents an ideal candidate for thrombosis. Recently, we showed that <sup>64</sup>Cu-DOTA–labeled PET probes based on fibrin-specific peptides are suitable vivo; however, the metabolic stability these was limited. Here, describe 4 new using either <sup>64</sup>Cu or aluminum fluoride (Al<sup>18</sup>F) chelated to 2...
The diagnosis of deep venous thromboembolic disease is still challenging despite the progress current thrombus imaging modalities and new diagnostic algorithms. We recently reported high target uptake efficacy novel fibrin-specific PET probe <sup>64</sup>Cu-FBP8. Here, we tested feasibility <sup>64</sup>Cu-FBP8 to detect source thrombi culprit emboli after vein thrombosis pulmonary embolism (DVT-PE). To support clinical translation <sup>64</sup>Cu-FBP8, performed a human dosimetry estimation...
Photoactivated drugs provide an opportunity to improve efficacy alongside reducing side-effects in the treatment of severe diseases such as cancer. Described herein is a photoactivation decaging method isobutylene-caged thiols through UV-initiated thiol-ene reaction. The was demonstrated with cysteine, cyclic disulfide-peptide, and thiol-containing drug, all which were rapidly efficiently released under mild UV irradiation presence thiol sources photoinitiator. Importantly, it shown that...
We have developed [2.2.1]azabicyclic vinyl sulfone reagents that simultaneously enable cysteine-selective protein modification and introduce a handle for further bioorthogonal ligation. The reaction is fast selective cysteine relative to other amino acids nucleophilic side-chains, the formed products are stable in human plasma moderately resistant retro Diels-Alder degradation reactions. A model biotinylated reagent was shown efficiently label two cysteine-tagged proteins, ubiquitin C2Am,...
In addition to its use for the study of biomolecules in living systems, bioorthogonal chemistry has emerged as a promising strategy enable protein or drug activation spatially and temporally controlled manner. This demonstrates application inverse electron-demand Diels-Alder (iEDDA) reaction cleave trans-cyclooctene (TCO) vinyl protecting groups from carboxylic acid-containing molecules. The tetrazine-mediated decaging proceeded under biocompatible conditions with fast kinetics (<2 min)....