Robin T. Aplin
University of Oxford
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Robin T. Aplin.
Tetrahedron-asymmetry | 1992
Norbert Sewald; Johann Lepschy von Gleissenthall; Manfred Schuster; Gerhard Müller; Robin T. Aplin
Abstract 3-β-D-Glucopyranosyl-4-desoxynivalenol, a glucoconjugate of the trichothecene 4-desoxynivalenol was isolated as main metabolite of DON from Zea mays suspension cultures. The structure was elucidated by two-dimensional NMR spectroscopy and electrospray mass spectroscopy.
Tetrahedron Letters | 1999
Timothy D. W. Claridge; Daniel D. Long; Natasha L. Hungerford; Robin T. Aplin; Martin D. Smith; Daniel G. Marquess; George W. J. Fleet
Abstract The efficient synthesis of an octameric furanose carbopeptoid, readily purified by chromatography in ethyl acetate:hexane (2:1), is reported. Extensive NMR studies suggest that two tetrameric 5-aminomethyltetrahydrofuran-2-carboxylates are prone to adopt solution conformations reminiscent of a repeating β-turn, a third tetramer and the corresponding octamer may tend towards a left-handed α-helix.
Tetrahedron-asymmetry | 1997
Thomas M. Krülle; Carmen de la Fuente; Lea Pickering; Robin T. Aplin; Katerina E. Tsitsanou; Spyros E. Zographos; Nikos G. Oikonomakos; Robert J. Nash; Rhodri C. Griffiths; George W. J. Fleet
Abstract Triazole-carboxylic acids related to d -glucose and d -galactose may be prepared by intramolecular [1,3]-dipolar cycloadditions of azides to unsaturated esters, followed by bromine oxidation of the resulting triazoline. Such materials may provide a series of anionic mimics of carbohydrates.
Biochemical Journal | 2004
David E. Lancaster; Luke A. McNeill; Michael A. McDonough; Robin T. Aplin; Kirsty S. Hewitson; Christopher W. Pugh; Peter J. Ratcliffe; Christopher J. Schofield
HIF (hypoxia-inducible factor) is an alphabeta transcription factor that modulates the hypoxic response in many animals. The cellular abundance and activity of HIF-alpha are regulated by its post-translational hydroxylation. The hydroxylation of HIF is catalysed by PHD (prolyl hydroxylase domain) enzymes and FIH (factorinhibiting HIF), all of which are 2-oxoglutarate- and Fe(II)-dependent dioxygenases. FIH hydroxylates a conserved asparagine residue in HIF-alpha (Asn-803), which blocks the binding of HIF to the transcriptional co-activator p300, preventing transcription of hypoxia-regulated genes under normoxic conditions. In the present paper, we report studies on possible mechanisms for the regulation of FIH activity. Recently solved crystal structures of FIH indicate that it is homodimeric. Site-directed mutants of FIH at residues Leu-340 and Ile-344, designed to disrupt dimerization, were generated in order to examine the importance of the dimeric state in determining FIH activity. A single point mutant, L340R (Leu-340-->Arg), was shown to be predominantly monomeric and to have lost catalytic activity as measured by assays monitoring 2-oxoglutarate turnover and asparagine hydroxylation. In contrast, the I344R (Ile-344-->Arg) mutant was predominantly dimeric and catalytically active. The results imply that the homodimeric form of FIH is required for productive substrate binding. The structural data also revealed a hydrophobic interaction formed between FIH and a conserved leucine residue (Leu-795) on the HIF substrate, which is close to the dimer interface. A recent report has revealed that phosphorylation of Thr-796, which is adjacent to Leu-795, enhances the transcriptional response in hypoxia. Consistent with this, we show that phosphorylation of Thr-796 prevents the hydroxylation of Asn-803 by FIH.
Structure | 2006
Christoph Meier; A. Radu Aricescu; René Assenberg; Robin T. Aplin; Robert J. C. Gilbert; Jonathan M. Grimes; David I. Stuart
Summary To achieve the greatest output from their limited genomes, viruses frequently make use of alternative open reading frames, in which translation is initiated from a start codon within an existing gene and, being out of frame, gives rise to a distinct protein product. These alternative protein products are, as yet, poorly characterized structurally. Here we report the crystal structure of ORF-9b, an alternative open reading frame within the nucleocapsid (N) gene from the SARS coronavirus. The protein has a novel fold, a dimeric tent-like β structure with an amphipathic surface, and a central hydrophobic cavity that binds lipid molecules. This cavity is likely to be involved in membrane attachment and, in mammalian cells, ORF-9b associates with intracellular vesicles, consistent with a role in the assembly of the virion. Analysis of ORF-9b and other overlapping genes suggests that they provide snapshots of the early evolution of novel protein folds.
FEBS Letters | 1990
Robin T. Aplin; Jack E. Baldwin; Christopher J. Schofield; Stephen G. Waley
Electrospray mass spectrometry was used to directly observe intact acyl enzyme complexes formed between a class C β‐lactamase (from Enterobacter cloacae P99) and four poor substrates/inhibitors. In each case the molecular weight difference between the unreacted and the reacted β‐lactamase was consistent with the formation of an acyl enzyme.
Tetrahedron-asymmetry | 1994
Benedicte Guilbert; Nicola J. Davis; Melanie Pearce; Robin T. Aplin; Sabine L. Flitsch
Abstract Sulfated mono- and disaccharides were synthesised by a novel sulfation method via regioselective activation of the saccharides to their dibutyltin stannylene acetals, followed by treatment with sulfur trioxidetrimethylamine. This methodology was applied to the synthesis of 3′-sulfated lactosides 15 and 23 , galactosylceramide sulfatide 3 and 2′-sulfated maltosides 30, 32 and 34 .
Chemical Communications | 2000
Jonathan J. Turnbull; Wendy J. Sobey; Robin T. Aplin; Abby Hassan; John L. Firmin; Christopher J. Schofield; Andy G. Prescott
Anthocyanidin synthase catalyses the in vitro conversion of its natural substrate, leucocyanidin, to cis- and trans-dihydroquercetin, quercetin and a small amount of cyanidin; incubation of trans-dihydroquercetin gave quercetin.
Tetrahedron | 1991
Jack E. Baldwin; Robert M. Adlington; Nicholas P. Crouch; Christopher J. Schofield; Nicholas J. Turner; Robin T. Aplin
Abstract Incubation of penicillin N ( 3a ) with partially purified deacetoxy/deacetylcephalosporin C synthase (DAOC/DAC synthase) from Cephalosporium acremonium CO 728 gave in addition to the expected products, deacetoxycephalosporin C and deacetylcephalosporin C, a third β-lactam metabolite as a 3β-hydroxy-3α-methylcepham ( 9a ). Production of the 3β-hydroxycepham was promoted from [3- 2 H]penicillin N ( 3b ) which was rationalised by the operation of a kinetic isotope effect on a branched pathway in the enzymic process. The oxygen of the 3β-hydroxy group was shown to be derived in part from molecular oxygen. In addition, the 2β-methyl group of penicillin N was shown to be incorporated into C2 of the 3β-hydroxy-3α-methylcepham, a result in stereochemical accord with the equivalent transformation of the 2β-methyl group of penicillin N into C2 of deacetoxycephalosporin C 1 . A mechanistic interpretation, consistent with these observations, is offered.
FEBS Letters | 1992
Kevin J. Lumb; Robin T. Aplin; Sheena E. Radford; David B. Archer; David J. Jeenes; Nigel Lambert; Donald A. MacKenzie; Christopher M. Dobson; Gordon Lowe
The production of a mutant hen lysozyme is described in which Asp‐52, one of the catalytically important residues, is replaced by Ser. The mutant enzyme has very low catalytic activity but NMR studies show that its structure is closely similar to that of the wild‐type protein. NMR experiments also show that well defined complexes are formed with GlcNAc4 and GlcNAc6 bound in the active Site of the mutant enzyme. Then complexes have been examined using electrospray mass spectrometry (ESMS). The most intense peaks arise from the uncomplexed protein indicating that dissociation takes place in the mass spectrometer under the conditions used here. Peaks from minor species corresponding to complexes between the protein and the oligosaccharides are, however, also observed. The possibility that the latter arise from novel covalent enzyme‐saccharide complexes is discussed.