A5030993266- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Medical Imaging Techniques and Applications
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- Legume Nitrogen Fixing Symbiosis
- Pharmacological Receptor Mechanisms and Effects
- Monoclonal and Polyclonal Antibodies Research
- Microbial Natural Products and Biosynthesis
- Cell Adhesion Molecules Research
- Neuroscience and Neuropharmacology Research
- Radiopharmaceutical Chemistry and Applications
- Cannabis and Cannabinoid Research
- RNA Interference and Gene Delivery
- Nanoplatforms for cancer theranostics
- Infant Nutrition and Health
- Amino Acid Enzymes and Metabolism
- Adenosine and Purinergic Signaling
- Synthetic Organic Chemistry Methods
- Synthesis of β-Lactam Compounds
- Advanced NMR Techniques and Applications
- RNA modifications and cancer
- Receptor Mechanisms and Signaling
University of Aberdeen
2015-2024
Institute of Medical Sciences
2015-2023
University of Milan
2007-2022
Molina Center for Energy and the Environment
2022
Sardegna Ricerche (Italy)
2012
A bacterial membrane protein, BacA, protects Sinorhizobium meliloti against the antimicrobial activity of host peptides, enabling peptides to induce persistence rather than death.
The first generation of CB1 positive allosteric modulators (e.g., ZCZ011) featured a 3-nitroalkyl-2-phenyl-indole structure. Although small number drugs include the nitro group, it is generally not regarded as being "drug-like", and this particularly true for aliphatic groups. There are very few case studies where an appropriate bioisostere replaced group that had direct role in binding. This may be indicative difficulty replicating its binding interactions. Herein, we report design...
Abstract A metabotropic glutamate receptor coupled to phospholipase D (PLD‐mGluR) was discovered in the hippocampus over three decades ago. Its pharmacology and direct linkage PLD activation are well established indicate it is a highly atypical receptor. with same present spindle primary sensory terminals where its blockade can totally abolish, double, normal stretch‐evoked firing. We report here first identification of this PLD‐mGluR protein, by capitalizing on expression mechanosensory...
[18F]-5-Fluoro-5-deoxyribose ([18F]-FDR) conjugates much more rapidly than [18F]-FDG under mild reaction conditions to peptides and offers new prospects for rapid bioconjugation fluorine-18 labelling in PET imaging.
The utility of 5-fluoro-5-deoxyribose (FDR) as an efficient bioconjugation agent for radiolabelling the RGD peptides c(RGDfK) and c(RGDfC) is demonstrated. significantly superior to that achieved with 2-fluoro-2-deoxyglucose (FDG) benefits from location fluorine at C-5, ribose a 5-membered ring sugar rather than 6-membered ring. Both features favour opening aldehydic form promote smooth oxime ligation aminooxy ether functionalised peptides. [18F]FDR was prepared in this study by synthesis...
Cyclic CNGRC (cCNGRC) peptides are very important targeting ligands for Aminopeptidase N (APN or CD13), which is overexpressed on the surface of many cancer cells. In this work we have (1) developed an efficient solid-phase synthesis and (2) tested purified porcine APN APN-expressing human cells two different classes cCNGRC peptides: first carrying a biotin affinity tag fluorescent attached to carboxyl Arg-Cys-COOH terminus second with tags amino H2N-Cys-Asn terminus. Carboxyl-terminus...
Aromatic prenyltransferases from cyanobactin biosynthetic pathways catalyse the chemoselective and regioselective intramolecular transfer of prenyl/geranyl groups isoprene donors to an electron-rich position in these macrocyclic linear peptides. These enzymes often demonstrate relaxed substrate specificity are considered useful biocatalysts for structural diversification Herein, we assess donor N1-tryptophan prenyltransferase AcyF anacyclamide A8P pathway using a library 22 synthetic alkyl...
We report a last-step fluorinase-catalyzed [(18) F]-fluorination of cysteine-containing RGD peptide. The peptide was attached through sulfur to modified and more hydrophilic variant the recently disclosed Barbas linker which itself linked chloroadenosine moiety via PEGylated chain. fluorinase able use this construct as substrate for transhalogenation reaction generate F]-radiolabeled peptides, retained high affinity cancer-cell relevant αv β3 integrins.
Arginine analogues incorporating carboxylate bioisosteric functional groups exhibit low micromolar inhibitory potential against human dimethylarginine dimethylaminohydrolase (DDAH), a key enzyme in the nitric oxide pathway.
Biochemical characterization of the prenyltransferase (AutF) from autumnalamide pathway shows it targets nitrogen guanidinium moiety in arginine and homoarginine.
Molecular imaging of αvβ3 integrin has exhibited real potential to guide the appropriate use anti-angiogenic therapies. However, an incomplete understanding factors that influence binding integrin-specific radiotracers currently limits their for assessing response therapy in cancer patients. This study identifies two fundamental modulate uptake these radiotracers. Procedures Experiments were performed prostate (PC3) and glioblastoma (U87MG) cells, which differentially express integrin. used...
The A2A adenosine receptor belongs to a family of G-coupled protein receptors that have been subjected extensive investigation over the last few decades. Due their prominent role in biological functions heart, lungs, CNS and brain, they become target for treatment illnesses ranging from cancer immunotherapy Parkinson's disease. imaging such by using positron emission tomography (PET) has also interest, potentially providing valuable tool analysing diagnosing various myocardial...
Synthetic tubulysins 24 a-m, containing non-hydrolysable N-substituents on tubuvaline (Tuv), were obtained in high purity and good overall yields using a multistep synthesis. A key step was the formation of differently N-substituted Ile-Tuv fragments 10 by an aza-Michael reaction azido-Ile derivatives 8 with α,β-unsaturated oxo-thiazole 5. structure-activity relationship study panel human tumour cell lines showed strong anti-proliferative activity for all compounds IC50 values sub-nanomolar...
Nonpeptidic Arg-Gly-Asp (RGD)-mimic ligands were designed and synthesized by click chemistry between an arginine-azide mimic aspartic acid-alkyne mimic. Some of these molecules combine excellent in vitro properties (high αv β3 affinity, selectivity, drug-like logD, high metabolic stability) with a variety radiolabeling options (e.g., tritium fluorine-18, plus compatibility radio-iodination), not requiring the use chelators or prosthetic groups. The binding mode resulting triazole RGD mimics...
The use of radiolabelled antibodies and antibody-derived recombinant constructs has shown promise for both imaging therapeutic use. In this context, the biotin-avidin/streptavidin pairing, along with inverse-electron-demand Diels-Alder (iEDDA) reaction, have found application in pretargeting approaches positron emission tomography (PET). This study reports fluorinase-mediated transhalogenation [5'-chloro-5'-deoxyadenosine (ClDA) substrates to 5'-fluoro-5'-deoxyadenosine (FDA) products] two...
FDA-PEG-GUL was enzymatically synthesised using the fluorinase in<sup>18</sup>F-radiolabelled form and shown to efficiently bind prostate-specific antigen (PSMA) which is upregulated in prostate cancer cells.
Abstract Objective The purpose of the study was to determine extent and role systemic hypoxia in pathogenesis spinal muscular atrophy (SMA). Methods Hypoxia assayed vivo early‐symptomatic (postnatal day 5) SMA‐model mice by pimonidazole [ 18 F]‐Fluoroazomycin arabinoside injections, which accumulate hypoxic cells, followed immunohistochemistry tracer biodistribution evaluation. Glucose uptake cells F]‐Fluorodeoxyglucose labeling. In vitro knockdown Survival Motor Neuron (SMN) performed on...
Hyperpolarization enhances the intensity of NMR signals a molecule, whose in vivo metabolic fate can be monitored by MRI with higher sensitivity. SABRE is hyperpolarization technique that could potentially used to image nitric oxide (NO) production vivo. This would very important, because NO dysregulation involved several pathologies, including cardiovascular ones. The synthase (NOS) pathway leads via conversion l-arginine into l-citrulline. free radical gas short half-life (≈5s), therefore...
The tetrazine/trans-cyclooctene (TCO) inverse electron-demand Diels-Alder (IEDDA) reaction is the fastest bioorthogonal "click" ligation process reported to date. In this context, TCO reagents have found widespread applications; however, their availability and structural diversity still somewhat limited due challenges connected with synthesis modification. To address issue, we developed a novel strategy for conjugation of derivatives biomolecule, which allows creation greater from single...