A5073311225- Chemical Synthesis and Reactions
- Chemical Synthesis and Analysis
- Protein Structure and Dynamics
- Carbohydrate Chemistry and Synthesis
- Sulfur-Based Synthesis Techniques
- Lipid Membrane Structure and Behavior
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Synthesis and biological activity
- Synthesis of Organic Compounds
- Receptor Mechanisms and Signaling
- Glycosylation and Glycoproteins Research
- Asymmetric Synthesis and Catalysis
- Fluorine in Organic Chemistry
- Synthesis of heterocyclic compounds
- Multicomponent Synthesis of Heterocycles
- Enzyme Structure and Function
- Cardiovascular Disease and Adiposity
- Synthesis and Reactions of Organic Compounds
- Computational Drug Discovery Methods
- Bioactive Compounds and Antitumor Agents
- Organic and Inorganic Chemical Reactions
- Vanadium and Halogenation Chemistry
- Marine Sponges and Natural Products
- Phytochemistry and Biological Activities
- Synthesis and pharmacology of benzodiazepine derivatives
Sukkur IBA University
2021-2025
East Carolina University
2022
University College Dublin
2007-2018
Trinity College Dublin
2011-2014
Google (United States)
2014
University of Tübingen
2002-2011
University of Karachi
1999-2011
International Center for Chemical and Biological Sciences
1999-2011
William Harvey Research Institute
2007
Leibniz Institute for Neurobiology
2006
X-ray crystallography of G protein-coupled receptors and other membrane proteins is hampered by difficulties associated with growing sufficiently large crystals that withstand radiation damage yield high-resolution data at synchrotron sources. We used an x-ray free-electron laser (XFEL) individual 50-femtosecond-duration pulses to minimize obtained a room-temperature structure human serotonin receptor using sub-10-micrometer microcrystals grown in mimetic matrix known as lipidic cubic phase....
The let-7 miRNA family plays a key role in modulating inflammatory responses. Vascular smooth muscle cell (SMC) proliferation and endothelial (EC) dysfunction are critical the pathogenesis of atherosclerosis, including setting diabetes. Here we report that levels decreased diabetic human carotid plaques model diabetes-associated ApoE-/- mouse. In vitro platelet-derived growth factor (PDGF)- tumor necrosis factor-α (TNF-α)-induced vascular SMC EC activation was associated with reduced...
Lipoxins, which are endogenously produced lipid mediators, promote the resolution of inflammation, and may inhibit fibrosis, suggesting a possible role in modulating renal disease. Here, lipoxin A4 (LXA4) attenuated TGF-β1–induced expression fibronectin, N-cadherin, thrombospondin, notch ligand jagged-1 cultured human proximal tubular epithelial (HK-2) cells through mechanism involving upregulation microRNA let-7c. Conversely, TGF-β1 suppressed In pretreated with LXA4, let-7c persisted...
Scientific Report10 June 2014Open Access Structural basis for polyspecificity in the POT family of proton-coupled oligopeptide transporters Joseph A Lyons Schools Medicine and Biochemistry & Immunology, Trinity College Dublin, Ireland Search more papers by this author Joanne L Parker Department Biochemistry, University Oxford, UK Nicolae Solcan Alette Brinth Dianfan Li Syed TA Shah Martin Caffrey Corresponding Author Simon Newstead Information Lyons1,3,‡, Parker2,‡, Solcan2, Brinth1, Li1,...
Increasing evidence points to the fact that defects in resolution of inflammatory pathways predisposes individuals development chronic diseases, including diabetic complications such as accelerated atherosclerosis. The inflammation is dynamically regulated by production endogenous modulators inflammation, lipoxin A4 (LXA4). Here, we explored therapeutic potential LXA4 and a synthetic LX analog (Benzo-LXA4) modulate streptozotocin-induced ApoE−/− mouse human carotid plaque tissue ex vivo....
Background The failure of spontaneous resolution underlies chronic inflammatory conditions, including microvascular complications diabetes such as diabetic kidney disease. identification endogenously generated molecules that promote the physiologic inflammation suggests these bioactions may have therapeutic potential in context inflammation. Lipoxins (LXs) are lipid mediators Methods We investigated LXA 4 and a synthetic LX analog (Benzo-LXA ) therapeutics murine model disease, ApoE −/− mice...
Lipoxins are a group of biologically active eicosanoids typically formed by transcellular lipoxygenase activity. Lipoxin A4 (LXA4) and B4 (LXB4) biosynthesis has been detected in variety inflammatory conditions. The native lipoxins LXA4 LXB4 demonstrate potent antiinflammatory proresolution bioactions. However, their therapeutic potential is compromised rapid metabolic inactivation PG dehydrogenase-mediated oxidation reduction. Here we report on the stereoselective synthesis aromatic...
The lipidic mesophase or in meso method for crystallizing membrane proteins has several high profile targets to its credit and is growing popularity. Despite success, the infancy as far rational crystallogenesis concerned. Consequently, significant time, effort, resources are still required generate structure-grade crystals, especially with a new target type. Therefore, need exists protocols that effective broad range of protein types. Recently, strategy prokaryotic α-helical protein,...
The NHC-Se scaffold has emerged as an intriguing target, opening new avenues for discovering compounds that could significantly improve public health. Recently, extensive efforts have been made to synthesize NHC-Se-based organic various biomedical applications. Herein, we disclose a straightforward method access series of N-heterocyclic carbene (NHC)-derived organoselenium molecules functionalized with amide moiety. parent adduct pendent ester moiety is sufficiently activated facilitate...
Magnesium is the most abundant divalent cation in living cells and crucial to several biological processes. MgtE a Mg(2+) channel distributed all domains of life that contributes maintenance cellular homeostasis. Here we report high-resolution crystal structures transmembrane domain MgtE, bound Mg(2+), Mn(2+) Ca(2+). The Mg(2+)-bound structure clearly visualized hydrated ion within its selectivity filter. Based on those biochemical analyses, propose mechanism for which geometry hydration...
Abstract A method for the parallel solid‐phase synthesis of peptide aldehydes has been developed. Protected amino acid obtained by racemization‐free oxidation alcohols with Dess–Martin periodinane were immobilized on threonyl resins as oxazolidines. Following Boc protection ring nitrogen to yield N‐protected oxazolidine linker, was performed efficiently this resin. aldehyde library designed targeting SARS coronavirus main protease, SARS‐CoV M pro (also known 3CL ), basis three different...
A systematic study of the crystallization an α-helical, integral membrane enzyme, diacylglycerol kinase, DgkA, using lipidic cubic mesophase or in meso method is described. These trials have resulted production blocky, rhombohedron-shaped crystals diffraction quality currently use for structure determination. Dramatic improvements crystal were obtained when identity lipid used to form bilayer into which protein was reconstituted as a prelude crystallogenesis varied. monoacylglycerol lipids...
A catalytic quantity of ZrCl 4 (20 mol %) was found to be an efficient catalyst for the one-pot esterification and deprotection (5 S,6 R)-5,6-diacetoxyoct-7-enoic acid in good yields (44-62%) with a lactone formed as minor byproduct. (10-20 also sufficient deprotect 1,3-dioxalane, bis-TBDMS ethers, diacetate functional groups excellent up 93%. (1-10 promoted diol protection acetonide 90% yield acted trans-esterification range esters.
The lipid-based bicontinuous cubic mesophase is a nanoporous membrane mimetic with applications in areas that include medicine, personal care products, foods and the basic sciences. An application of particular note concerns it use as medium which to grow crystals proteins for structure determination by X-ray crystallography. At least two variations exist. One highly viscous phase, has well developed long-range order. other so-called sponge phase considerably more fluid lacks recently been...
A novel microwave-assisted, chemoselective and efficient method for the cleavage of silyl ethers (aliphatic aromatic) catalyzed by Selectfluor is reported. wide range TBS-, TIPS-, TBDPS-protected alkyl can be chemoselectively cleaved in high yield presence aryl ethers. The deprotection phenolic TBS ethers, not TIPS- or esters were also achieved under these reaction conditions. In addition, transetherification etherification benzylic hydroxy groups alcoholic solvents observed.