A5026431273- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Microtubule and mitosis dynamics
- Hydrocarbon exploration and reservoir analysis
- RNA and protein synthesis mechanisms
- Developmental Biology and Gene Regulation
- Photosynthetic Processes and Mechanisms
- Zebrafish Biomedical Research Applications
- Neurobiology of Language and Bilingualism
- Reading and Literacy Development
- Cell death mechanisms and regulation
- Ubiquitin and proteasome pathways
- Atmospheric and Environmental Gas Dynamics
- Gene Regulatory Network Analysis
- Cancer-related Molecular Pathways
- Cellular transport and secretion
- Protist diversity and phylogeny
- Carbohydrate Chemistry and Synthesis
- Geological Studies and Exploration
- Hedgehog Signaling Pathway Studies
- Advanced biosensing and bioanalysis techniques
- Pluripotent Stem Cells Research
- Geochemistry and Geologic Mapping
- DNA Repair Mechanisms
- Monoclonal and Polyclonal Antibodies Research
Institute of Structural and Molecular Biology
2014-2024
University of Leeds
2014-2024
The Honourable Society of Lincoln's Inn
2011-2015
Dabur (India)
2015
Sappasithiprasong Hospital
2015
Cancer Research UK
2011-2014
Ottawa Hospital
1999-2002
Western Regional Research Center
2002
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2001
National Institutes of Health
1999-2001
The zebrafish is an excellent genetic system for the study of vertebrate development and disease. In effort to provide a rapid robust tool gene mapping, panel radiation hybrids (RH) was produced by fusion irradiated AB9 cells with mouse B78 cells. overall retention sequences in 93 RH cell lines that constitute LN54 22%. Characterization 849 simple sequence length polymorphism markers, 84 cloned genes 122 expressed tags allowed production map whose total size 11,501 centiRays. From this...
Amputation of the zebrafish caudal fin stimulates regeneration dermal skeleton and reexpression sonic hedgehog (shh)-signaling pathway genes. Expression patterns suggest a role for shh signaling in secretion patterning regenerating bone, but direct has not been demonstrated. We established an vivo method gene transfection to express ectopically genes blastema fins. Ectopic expression or bmp2 blastema-induced excess bone deposition altered regenerate. The effects ectopic could be antagonized...
Abstract Inhibition of protein–protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. α‐Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed “proteomimetics”, which can assembled modular manner reproduce the vectoral presentation key side chains found on helical motif from one partner within PPI. In this work, it is demonstrated that by library N‐alkylated aromatic oligoamide helix mimetics, potent mimetics their...
A versatile, rapid and reversible approach to constrain peptides in a bioactive helical conformation bearing functional handle for inhibition of protein–protein interactions is described.
The combination of an E2 ubiquitin-conjugating enzyme with E3 ubiquitin-ligase is essential for ubiquitin modification a substrate. Moreover, the pairing dictates both substrate choice and type. molecular details generic E3-E2 interactions are well established. Nevertheless, determinants selective, specific recognition not understood. There ∼40 E2s ∼600 E3s giving rise to possible ∼24,000 pairs. Using Fanconi Anemia pathway exclusive pair, FANCL-Ube2T, we report atomic structure FANCL...
Biophysical studies on hydrocarbon constrained peptides reveal induced fit binding and enthalpy–entropy compensation target protein recognition.
Abstract A major current challenge in bioorganic chemistry is the identification of effective mimics protein secondary structures that act as inhibitors protein–protein interactions (PPIs). In this work, trans ‐2‐aminocyclobutanecarboxylic acid ( t ACBC) was used key β‐amino component design α/β/γ ‐ peptides to structurally mimic a native α‐helix. Suitably functionalized α/β/γ‐peptides assume an α‐helix‐mimicking 12,13‐helix conformation solution, exhibit enhanced proteolytic stability...
An oligoamide helix mimicking foldamer with well-defined conformation is shown to recognize its target protein <italic>h</italic>DM2 in a manner that depends upon the composition, spatial projection and stereochemistry of functional groups appended scaffold.
The Fanconi anemia (FA) pathway is essential for the repair of DNA interstrand cross-links. At heart this monoubiquitination FANCI-FANCD2 (ID) complex by multiprotein "core complex" containing E3 ubiquitin ligase FANCL. Vertebrate organisms have eight-protein core complex, whereas invertebrates apparently do not. We report here structure central domain human FANCL in comparison with recently solved Drosophila melanogaster Our data represent first structural detail into catalytic system and...
To increase the density of a gene map zebrafish, Danio rerio , we have placed 3119 expressed sequence tags (ESTs) and cDNA sequences on LN54 radiation hybrid (RH) panel. The ESTs genes mapped here join 748 SSLp markers 459 previously ESTs, bringing total number RH panel to 4226. Addition these new brings size 14,372 cR, with 118 kb/cR. distribution according linkage groups shows relatively little variation (minimum, 73; maximum, 201). This observation, combined uniform for zebrafish...
Abstract Normal and one subtype of disabled readers were compared in their visual eventrelated potentials (ERPs) that elicited by primed unprimed words during a recognition memory task. The preceded picture having the same denotative meaning, while non-associated meaning. exhibited consistently greater amplitude than to with negative wave at 455 ms (N400). For readers, this N400 was evident, though somewhat smaller, for controls, fronto-central placements, but absent lateral parietal...
Abstract Aurora-A is an essential cell-cycle kinase with critical roles in mitotic entry and spindle dynamics. These functions require binding partners such as CEP192 TPX2, which modulate both activity localisation of Aurora-A. Here we investigate the structure role centrosomal Aurora-A:CEP192 complex wider molecular network. We find that wraps around Aurora-A, occupies sites for spindle-associated partners, thus competes them. Comparison two different conformations reveals how modifies...
Summary The U.K. North Sea contains a wide variety of reservoired oils, ranging from the biodegraded heavy via mid-gravity crudes to light oils and condensates. Statistical data suite gives an average API gravity 36°, asphaltene content 1.4% saturate/aromatic ratio 2.02. Averages for pristane/phytane, pristane/n-C 17 phytane/n-C 18 are 1.24, 0.63 0.56 respectively. It is possible explain ocurrence vast majority in terms generation over range maturities single source rock horizons (the...
We present methodology to modify <italic>N</italic>-alkylated aromatic oligoamide α-helix mimetics using ‘click’ chemistry.
Abstract Inhibition of protein–protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. α‐Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed “proteomimetics”, which can assembled modular manner reproduce the vectoral presentation key side chains found on helical motif from one partner within PPI. In this work, it is demonstrated that by library N‐alkylated aromatic oligoamide helix mimetics, potent mimetics their...
// Li-Juan Liu 1 , Bingyong He 2 Jennifer A. Miles 3, 4 Wanhe Wang Zhifeng Mao Weng Ian Che Jin-Jian Lu Xiu-Ping Chen Andrew J. Wilson Dik-Lung Ma Chung-Hang Leung State Key Laboratory of Quality Research in Chinese Medicine, Institute Medical Sciences, University Macau, Macao, China Department Chemistry, Hong Kong Baptist University, Kong, 3 School Leeds, UK Astbury Centre for Structural Molecular Biology, Correspondence to: Leung, e-mail: duncanleung@umac.mo Ma, edmondma@hkbu.edu.hk...
The Viking (Graben of the North Sea contains a major deltaic reservoir-the Brent Group. Within Group, Etive Formation, coastal barrier sand, is both areally continuous and has excellent porosity permeability. It sandwiched between fine-grained micaceous sandstones Rannoch Formation below impermeable mudstones Ness above. Consequently, acted as most important regional conduit for secondary migration Upper Jurassic sourced oils. Oil through time left heavy residue in uppermost part formation....
Abstract Three learning-disability (LD) subtype groups and a normal control group of children were compared in their visual event-related potentials (ERPs) to primed unprimed words. The LD subtypes defined by deficient performance on tests arithmetic (Group A), reading spelling RS), or both RSA). words preceded pictures spoken having related meaning, while non-associated For controls, N450 amplitude was greater than Group A, reduced spoken-word primes, but not picture an effect that...
Pathogenic antiphospholipid antibodies (aPL) cause the syndrome (APS) by interacting with domain I (DI) of beta-2-glycoprotein (β2GPI). The aPL/β2GPI complex then exerts pathogenic effects on target cells. We previously described periplasmic bacterial expression native and mutated variants DI, reported presence immunodominant epitopes at positions 8–9 (D8/D9) position 39 (R39). Mutations these strongly influenced ability recombinant DI to bind patient-derived IgG aPL inhibit in a mouse model...
The exploitation of multivalent ligands for the inhibition protein-protein interactions has not yet been explored as a supramolecular design strategy. This is despite fact that typically occur within context multi-protein complexes and frequently exploit avidity effects or co-operative binding to achieve high affinity interactions. In this paper we describe preliminary studies on use N-alkylated aromatic oligoamide helix mimetic p53/hDM2 establish protein dimerisation promoted, rather than...
Foldamers are abiotic molecules that mimic the ability of bio-macromolecules to adopt well-defined and organised secondary, tertiary or quaternary structure. Such templates have enabled generation defined architectures which present structurally surfaces can achieve molecular recognition diverse complex targets. Far less explored is whether this mimicry nature extend more advanced functions biological macromolecules such as activation catalytic function. In work, we a novel replacement...
Abstract : The BCL‐2 family is a challenging group of proteins to target selectively due sequence and structural homologies across the family. Selective ligands for regulators apoptosis are useful as probes understand cell biology apoptotic signalling pathways, starting points inhibitor design. We have used phage display isolate Affimer reagents (non‐antibody‐binding based on conserved scaffold) identify MCL‐1, BCL‐x L , BCL‐2, BAK BAX, then multiple biophysical characterisation methods...
Abstract A major current challenge in bioorganic chemistry is the identification of effective mimics protein secondary structures that act as inhibitors protein–protein interactions (PPIs). In this work, trans ‐2‐aminocyclobutanecarboxylic acid ( t ACBC) was used key β‐amino component design α/β/γ ‐ peptides to structurally mimic a native α‐helix. Suitably functionalized α/β/γ‐peptides assume an α‐helix‐mimicking 12,13‐helix conformation solution, exhibit enhanced proteolytic stability...
Using N-Myc