A5060881547- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Bacterial biofilms and quorum sensing
- Click Chemistry and Applications
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
- Antimicrobial Peptides and Activities
- Bacterial Genetics and Biotechnology
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Biochemical and Structural Characterization
- Nanoparticle-Based Drug Delivery
- Monoclonal and Polyclonal Antibodies Research
- Plant-Microbe Interactions and Immunity
- Synthesis and Characterization of Heterocyclic Compounds
- Gold and Silver Nanoparticles Synthesis and Applications
- Vibrio bacteria research studies
- Chemical Synthesis and Analysis
- Nanocluster Synthesis and Applications
- Nanomaterials for catalytic reactions
- Photochromic and Fluorescence Chemistry
University of Oxford
2018-2022
Science Oxford
2018-2020
University of Cambridge
2013-2017
Leiden University
2017
Abstract Oligonucleotides that target mRNA have great promise as therapeutic agents for life-threatening conditions but suffer from poor bioavailability, hence high cost. As currently untreatable diseases come within the reach of oligonucleotide therapies, new analogues are urgently needed to address this. With this in mind we describe reduced-charge oligonucleotides containing artificial LNA-amide linkages with improved gymnotic cell uptake, RNA affinity, stability and potency. To construct...
The opportunistic pathogen Pseudomonas aeruginosa utilises the cell-cell signalling mechanism known as quorum sensing to regulate virulence. P. produces two quinolone-based molecules; quinolone signal (PQS) and its biosynthetic precursor 2-heptyl-4(1H)-quinolone (HHQ). To date, only one receptor (the PqsR protein) has been identified that is capable of binding PQS HHQ. Here, we report on synthesis HHQ affinity probes for chemical proteomic studies. probe very effectively captured in vitro....
Recently reported DNA nanoflowers are an interesting class of organic-inorganic hybrid materials which prepared using polymerases. combine the high surface area and scaffolding inorganic Mg2P2O7 nanocrystals with targeting properties DNA, whilst adding enzymatic stability enhanced cellular uptake. We have investigated conditions for chemically modifying core these through substitution Mg2+ Mn2+, Co2+ or Zn2+ characterized resulting particles. These a range novel nanoarchitectures, retain...
Rolling circle amplification (RCA) is a powerful tool for the construction of DNA nanomaterials such as hydrogels, high-performance scaffolds and nanoflowers (DNFs), hybrid materials formed magnesium pyrophosphate. Such have great potential in therapeutics, imaging, protein immobilisation, drug delivery, yet limited chemistry available to expand their functionality. Here, we present orthogonal strategies produce densely modified RCA products DNFs. We provide methods selectively modify...
Three different chemical cyclisation reactions yield biocompatible cyclic oligonucleotide templates for use in RCA and DNA nanoflower formation.
Abstract Pseudomonas aeruginosa is an opportunistic human pathogen that routinely appears near the top of public health threat lists worldwide. P. causes infections by secreting a wealth exceptionally active exoproducts, leading to tissue damage. The synthesis many these virulence factors now known be under control quorum sensing (QS) system. Over last 15 years, quinolone signal (PQS) has been found play crucial role in QS linking two segments (las and rhl) N‐ acylhomoserine...
Photoaffinity labelling is a useful method for studying how proteins interact with ligands and biomolecules, can help identify characterise new targets the development of therapeutics. We present design synthesis novel multifunctional benzophenone linker that serves as both photo-crosslinking motif peptide stapling reagent. Using double-click stapling, we attached to via staple linker, rather than by modifying sequence amino acid. When applied p53-derived peptide, resulting photoreactive...
Design, synthesis and application of PQS HHQ probes for investigating quinolone quorum sensing pathways using photoaffinity labeling.
Triazole linkages (TLs) are mimics of the phosphodiester bond in oligonucleotides with applications synthetic biology and biotechnology. Here we report RuAAC-catalyzed synthesis a novel 1,5-disubstituted triazole (TL2) dinucleoside phosphoramidite as well its incorporation into compare DNA polymerase replication competency other TL analogues. We demonstrate that TL2 has superior kinetics to these analogues is accurately replicated by polymerases. Derived structure–biocompatibility...
Dinucleoside phosphoramidites containing a triazole internucleotide linkage flanked by locked nucleic acid (LNA) were synthesized and incorporated into oligonucleotides (ONs). ONs bearing both LNA at multiple sites obtained their biophysical properties including enzymatic stability binding affinity for RNA DNA targets studied. t-LNAs with four incorporations of dinucleoside monomer having on either side the bind to target significantly higher greater specificity than unmodified...
The combination of amide coupling with standard oligonucleotide synthesis enables assembly reduced charge chimeric gapmer antisense oligonucleotides that trigger an efficient RNase H response while improving serum lifetime and cellular uptake.
Pseudomonas aeruginosa is a human pathogen associated with variety of life-threatening nosocomial infections. This organism produces range virulence factors which actively cause damage to host tissues. One such factor pyocyanin, known play crucial role in the pathogenesis P. Previous studies had identified novel compound capable strongly inhibiting production pyocyanin. It was postulated that this inhibition results from modulation an intercellular communication system termed quorum sensing,...
Oligonucleotides are rapidly emerging as powerful therapeutics for hard to treat diseases. Short single-stranded oligonucleotides can base pair with target RNA and alter gene expression, providing an attractive therapeutic approach at the genetic level. Whilst conceptually appealing, require chemical modification clinical use. One is substitute phosphodiester backbone other linkages such triazole. The triazole linkage inherently resistant enzymatic degradation, stability in vivo, uncharged,...
Rolling circle amplification (RCA) is a powerful tool for the construction of DNA nanomaterials such as hydrogels, high-performance scaffolds and nanoflowers (DNFs), hybrid materials formed magnesium pyrophosphate. Such have great potential in therapeutics, imaging, protein immobilisation, drug delivery, yet limited chemistry available to expand their functionality. Here, we present an orthogonal strategy produce densely modified RCA products DNFs. We show that it possible selectively...
<p>Rolling circle amplification (RCA) is a powerful tool for the construction of DNA nanomaterials such as hydrogels, high-performance scaffolds and nanoflowers (DNFs), hybrid materials formed magnesium pyrophosphate. Such have great potential in therapeutics, imaging, protein immobilisation, drug delivery, yet limited chemistry available to expand their functionality. Here, we present an orthogonal strategy produce densely modified RCA products DNFs. We show that it possible...
Abstract Oligonucleotides that target mRNA have great promise as therapeutic agents for life-threatening conditions but suffer from poor bioavailability, hence high cost. As currently untreatable diseases come within the reach of oligonucleotide therapies, new analogues are urgently needed to address this. With this in mind we developed reduced-charge oligonucleotides containing artificial LNA-amide linkages with improved gymnotic cell uptake, RNA affinity, stability and potency. To...