A5031692113- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Microbial Natural Products and Biosynthesis
- Crystallography and molecular interactions
- Chemical Synthesis and Analysis
- Cancer therapeutics and mechanisms
- Synthesis and biological activity
- Crystal structures of chemical compounds
- Synthetic Organic Chemistry Methods
- Radiopharmaceutical Chemistry and Applications
- Computational Drug Discovery Methods
- Microbial Metabolism and Applications
- Molecular Sensors and Ion Detection
- Peptidase Inhibition and Analysis
- Mass Spectrometry Techniques and Applications
- Plant biochemistry and biosynthesis
- Cannabis and Cannabinoid Research
- Supramolecular Chemistry and Complexes
- Melanoma and MAPK Pathways
- Lipid Membrane Structure and Behavior
- Oxidative Organic Chemistry Reactions
- Marine Sponges and Natural Products
- Neurotransmitter Receptor Influence on Behavior
- Cholinesterase and Neurodegenerative Diseases
- Medical Imaging Techniques and Applications
University of Aberdeen
2015-2024
Marine Scotland
2024
UCLouvain
2000-2020
The Ohio State University
2016
Physical Sciences (United States)
2016
University of Surrey
2012
Scripps Research Institute
2003-2004
Alkanes adopt extended conformations in solution that minimize steric interactions and maximize surface area. Folding can reduce the amount of hydrophobic exposed to solvent, but sterically unfavorable gauche result. However, we found alkyl chains two common surfactants aqueous helical when bound within a synthetic receptor. The receptor recognizes alkane better than conformation, even though 2 3 kilocalories per mole strain is introduced. proper filling space burial drive molecular...
The reversible encapsulation of a series normal alkane guests in cylindrical host was studied by NMR methods. For small hydrocarbons such as n-pentane or n-hexane, two enter the host, and they move freely within. With n-heptane no takes place. longer alkanes n-decane, single guest enters aromatic walls are seen to twist avoid empty spaces increase favorable interactions with hydrocarbon. best (n-undecane) adopts conformation minimal gauche interactions. longest accommodated, n-tetradecane,...
The pharmacological exploitation of the galanin receptors as drug targets for treatment epilepsy, depression, and pain has been hampered by lack workable compounds medicinal chemists from random screening large chemical libraries. present work uses tripeptidomimetic galnon displays its presumed pharmacophores on a rigid molecular scaffold. scaffold is related to marine natural products presents three functional groups near one another in space, manner reminiscent protein surface. An active...
We describe here the synthesis and characterization of a molecular receptor that forms kinetically thermodynamically stable host−guest complexes in water. This cavitand-based host is composed preorganized aromatic pocket whose rim decorated with four negatively charged carboxylate groups. 1H NMR isothermal titration calorimetry have been used to characterize behavior resulting response changes pH, buffer identity, salt concentration presence sodium dodecyl sulfate micelles.
Doing the twist: Incorporation of long hydrocarbons during self-assembly a cylindrical capsule containing an elongated cavity lined with eight benzene rings and additional π surfaces induces helical conformations chains so that they are fully encapsulated within (see picture). Supporting information for this article is available on WWW under http://www.wiley-vch.de/contents/jc_2002/2003/z52235_s.pdf or from author. Please note: The publisher not responsible content functionality any...
Several allosteric modulators (AMs) of the CB1 receptor have been characterized in vitro, including Org27569, which enhances CB1-specific binding [H]CP55,940, but behaves as an insurmountable CB1-receptor antagonist several biochemical assays. Although a growing body research has investigated molecular actions this unusual AM, it is unknown whether these translate to whole animal. The purpose present study was determine Org27569 would produce effects well-established mouse behavioral assays...
Abstract Cyanobactins are a rapidly growing family of linear and cyclic peptides produced by cyanobacteria. Kawaguchipeptins A B, two macrocyclic undecapeptides reported earlier from Microcystis aeruginosa NIES‐88, shown to be products the cyanobactin biosynthetic pathway. The 9 kb kawaguchipeptin ( kgp ) gene cluster was identified in 5.26 Mb draft genome NIES‐88. We verified that this is responsible for production kawaguchipeptins through heterologous expression Escherichia coli . KgpF...
Abstract Pyrrolizidine alkaloids (PAs) are a group of natural products with important biological activities. The discovery and characterization the multifunctional FAD‐dependent enzyme LgnC is now described. shown to convert indolizidine intermediates into pyrrolizidines through an unusual ring expansion/contraction mechanism, catalyze biosynthesis new bacterial PAs, so‐called legonmycins. By genome‐driven analysis, heterologous expression, gene inactivation, legonmycins were also originate...
The apoptotic antiproliferative actions of our previously reported CB1 allosteric modulators 5-chlorobenzofuran-2-carboxamide derivatives VIIa-j prompted us to develop and synthesise a novel series indole-2-carboxamide 5a-k, 6a-c, 7. Different spectroscopic methods analysis were used validate the compounds. Using MTT assay method, compounds examined for activity against four distinct cancer cell lines. Compounds 7 demonstrated greater breast line (MCF-7) than other tested lines, 5a-k (which...
Mutant EGFR/BRAF pathways are thought to be crucial targets for the development of anticancer drugs since they over-activated in several malignancies. We present here a novel series 5-chloro-indole-2-carboxylate 3a–e, 4a–c and pyrrolo[3,4-b]indol-3-ones 5a–c derivatives as potent inhibitors mutant with antiproliferative activity. The cell viability assay results 4a–c, revealed that none compounds tested were cytotoxic, majority those at 50 µM had levels greater than 87%. Compounds...
Four negative charges at the entrance of a deep pocket, lined with aromatic residues are features synthetic receptor which shows high affinity for acetylcholine (see picture) and choline in water. The size, shape, charge recognition elements featured natural enzyme acetylcholinesterase reproduced by receptor.
Abstract Dehydroalanine (Dha) and dehydrobutyrine (Dhb) display considerable flexibility in a variety of chemical biological reactions. Natural products containing Dha and/or Dhb residues are often found to diverse activities. While the ( Z ) geometry is predominant nature, only handful metabolites E )‐Dhb have been thus far. Here we report discovery new antimicrobial peptide, albopeptide, through NMR analysis synthesis, which contains two contiguous unsaturated residues, Dha‐( )‐Dhb. It...
A new series of indole-2-carboxamides 5a-g, 6a-f and pyrido[3,4-b]indol-1-ones 7a 7b have been developed as antiproliferative agents that target both wild mutant type EGFR. The effect the compounds was studied. 5c, 5d, 5f, 5 g, 6e, 6f highest activity with GI50 values ranging from 29 nM to 47 in comparison reference erlotinib (GI50 = 33 nM). Compounds g inhibited EGFRWT IC50 68 85 while is 80 nM. Moreover, 5f had most potent inhibitory against EGFRT790M 9.5 ± 2 11.9 3 nM, respectively, being...
Two novel polyketides, accraspiroketides A (1) and B (2), which feature unprecedented [6 + 6+6 6] [5 5] spiro chemical architectures, were isolated from Streptomyces sp. MA37 ΔaccJ mutant strain. Compounds 1-2 exhibit excellent activity against Gram-positive bacteria (MIC = 1.5–6.3 μg/mL). Notably, 1 2 have superior clinically Enterococcus faecium K60–39 4.0 μg/mL 4.7 μg/mL, respectively) than ampicillin 25
The present study details the design, synthesis, and bio-evaluation of indoles
Abstract We describe for the first time synthesis of biocompatible TiO 2 nanoparticles containing a functional NH group which are easily dispersible in water. The water coated with mercaptosuccinic acid is also reported. show that it possible to exchange stearic from pre-synthesised fatty acid-coated anatase 5-nm range organic ligands no change size or morphology. With further functionalisation, these could be used medical imaging carry cytotoxic radionuclides radioimmunotherapy where...
Pulmonarins A and B are two new dibrominated marine acetylcholinesterase inhibitors that were isolated characterized from the sub-Arctic ascidian Synoicum pulmonaria collected off Norwegian coast. The structures of natural pulmonarins tentatively elucidated by spectroscopic methods later verified comparison with synthetically prepared material. Both displayed reversible, noncompetitive inhibition comparable to several known inhibitiors. Pulmonarin was strongest inhibitor, an constant (Ki) 20...
Abstract Ribosomally synthesized and post-translationally modified peptides (RiPPs) are structurally complex natural products with diverse bioactivities. Here we report discovery of a RiPP, kintamdin, for which the structure is determined through spectroscopy, spectrometry genomic analysis to feature bis -thioether macrocyclic ring β-enamino acid residue. Biosynthetic investigation demonstrated that its pathway relies on four dedicated proteins: phosphotransferase KinD, Lyase KinC, kinase...
The complexation of a water-soluble cavitand and sodium dodecyl sulfate micelles is studied using NMR diffusion ordered spectroscopy.
18F-fluorine is an ideal imaging PET (positron emission tomography) nuclide due to the low energy of its β+ (positron) and pure decay. PAMAM dendrimers are branched organic molecules with multiple NH2 termini each which can accommodate attachment functionalities. The presence a thiol group also facilitates conjugation targeting molecule. Here we describe boroaryl moieties terminal groups after cleavage bridging functionalized dendrons (half-dendrimers) biotin. Incubation targeted,...