Imperial College London

Emeritus ProfessorAndrewHolmes

Faculty of Natural SciencesDepartment of Chemistry

Distinguished Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 9286andrew.holmes Website

 
 
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Assistant

 

Ms Maria Tortelli +44 (0)20 7594 9286

 
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Location

 

Molecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Publication Type
Year
to

552 results found

Sandee AJ, Williams CK, Evans NR, Davies JE, Boothby CE, Köhler A, Friend RH, Holmes ABet al., 2004, Solution-processible conjugated electrophosphorescent polymers, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 126, Pages: 7041-7048, ISSN: 0002-7863

Journal article

Dove SK, Piper RC, McEwen RK, Yu JW, King MC, Hughes DC, Thuring J, Holmes AB, Cooke FT, Michell RH, Parker PJ, Lemmon MAet al., 2004, Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors., EMBO J, Vol: 23, Pages: 1922-1933, ISSN: 0261-4189

Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), made by Fab1p, is essential for vesicle recycling from vacuole/lysosomal compartments and for protein sorting into multivesicular bodies. To isolate PtdIns(3,5)P2 effectors, we identified Saccharomyces cerevisiae mutants that display fab1delta-like vacuole enlargement, one of which lacked the SVP1/YFR021w/ATG18 gene. Expressed Svp1p displays PtdIns(3,5)P2 binding of exquisite specificity, GFP-Svp1p localises to the vacuole membrane in a Fab1p-dependent manner, and svp1delta cells fail to recycle a marker protein from the vacuole to the Golgi. Cells lacking Svp1p accumulate abnormally large amounts of PtdIns(3,5)P2. These observations identify Svp1p as a PtdIns(3,5)P2 effector required for PtdIns(3,5)P2-dependent membrane recycling from the vacuole. Other Svp1p-related proteins, including human and Drosophila homologues, bind PtdIns(3,5)P2 similarly. Svp1p and related proteins almost certainly fold as beta-propellers, and the PtdIns(3,5)P2-binding site is on the beta-propeller. It is likely that many of the Svp1p-related proteins that are ubiquitous throughout the eukaryotes are PtdIns(3,5)P2 effectors. Svp1p is not involved in the contributions of FAB1/PtdIns(3,5)P2 to MVB sorting or to vacuole acidification and so additional PtdIns(3,5)P2 effectors must exist.

Journal article

Haque SA, Park T, Xu C, Koops S, Schulte N, Potter RJ, Holmes AB, Durrant JRet al., 2004, Interface engineering for solid-state dye-sensitized nanocrystalline solar cells: The use of ion-solvating hole-transporting polymers, ADVANCED FUNCTIONAL MATERIALS, Vol: 14, Pages: 435-440, ISSN: 1616-301X

Journal article

Horsley HT, Holmes AB, Davies JE, Goodman JM, Silva MA, Pascu SI, Collins Iet al., 2004, Investigation of conjugate addition/intramolecular nitrone dipolar cycloadditions and their use in the synthesis of dendrobatid alkaloid precursors., Org Biomol Chem, Vol: 2, Pages: 1258-1265, ISSN: 1477-0520

The sequential intramolecular conjugate addition of the oxime 13 followed by intramolecular dipolar cycloaddition of the intermediate nitrone 14 affords a mixture of the isoxazolidines 15, 16 and 17. The tricyclic 6,5,5-adduct 15 is believed to be the product of kinetic control and can be equilibrated with the epimeric tricyclic 6,5,5-isoxazolidine 17 through a beta-elimination/conjugate addition process. Conditions have been developed for the two-step conversion of the ketone 12 under thermodynamic control into the racemic tricyclic 6,6,5-adduct 16 which is the core precursor of all the known histrionicotoxin alkaloids.

Journal article

O'Sullivan PT, Buhr W, Fuhry MAM, Harrison JR, Davies JE, Feeder N, Marshall DR, Burton JW, Holmes ABet al., 2004, A concise synthesis of the octalactins., J Am Chem Soc, Vol: 126, Pages: 2194-2207, ISSN: 0002-7863

The total synthesis of octalactins A and B has been achieved in 15 steps (longest linear sequence) and 10% overall yield from commercially available materials. Key steps include the Paterson-Aldol reaction for the rapid assembly of the carbonate 46, methylenation of 46 and subsequent Claisen rearrangement of the corresponding alkenyl-substituted cyclic ketene acetal to provide the core unsaturated medium-ring lactone 47, and the use of enzyme-mediated acetate deprotection in the presence of a medium-ring lactone.

Journal article

Billington RA, Thuring JW, Conway SJ, Packman L, Holmes AB, Genazzani AAet al., 2004, Production and characterization of reduced NAADP (nicotinic acid-adenine dinucleotide phosphate)., Biochem J, Vol: 378, Pages: 275-280

The pyridine nucleotide NAADP (nicotinic acid-adenine dinucleotide phosphate) has been shown to act as a Ca2+-releasing intracellular messenger in a wide variety of systems from invertebrates to mammals and has been implicated in a number of cellular processes. NAADP is structurally very similar to its precursor, the endogenous coenzyme NADP and while much is known about the reduced form of NADP, NADPH, it is not known whether NAADP can also exist in a reduced state. Here we report that NAADP can be reduced to NAADPH by endogenous cellular enzymes and that NAADPH is functionally inert at the NAADP receptor. These data suggest that NAADPH could represent a mechanism for rapidly inactivating NAADP in cells.

Journal article

Kasri NN, Holmes AM, Bultynck G, Parys JB, Bootman MD, Rietdorf K, Missiaen L, McDonald F, De Smedt H, Conway SJ, Holmes AB, Berridge MJ, Roderick HLet al., 2004, Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins., EMBO J, Vol: 23, Pages: 312-321, ISSN: 0261-4189

Inositol 1,4,5-trisphosphate receptors (InsP(3)Rs) were recently demonstrated to be activated independently of InsP(3) by a family of calmodulin (CaM)-like neuronal Ca(2+)-binding proteins (CaBPs). We investigated the interaction of both naturally occurring long and short CaBP1 isoforms with InsP(3)Rs, and their functional effects on InsP(3)R-evoked Ca(2+) signals. Using several experimental paradigms, including transient expression in COS cells, acute injection of recombinant protein into Xenopus oocytes and (45)Ca(2+) flux from permeabilised COS cells, we demonstrated that CaBPs decrease the sensitivity of InsP(3)-induced Ca(2+) release (IICR). In addition, we found a Ca(2+)-independent interaction between CaBP1 and the NH(2)-terminal 159 amino acids of the type 1 InsP(3)R. This interaction resulted in decreased InsP(3) binding to the receptor reminiscent of that observed for CaM. Unlike CaM, however, CaBPs do not inhibit ryanodine receptors, have a higher affinity for InsP(3)Rs and more potently inhibited IICR. We also show that phosphorylation of CaBP1 at a casein kinase 2 consensus site regulates its inhibition of IICR. Our data suggest that CaBPs are endogenous regulators of InsP(3)Rs tuning the sensitivity of cells to InsP(3).

Journal article

Leeke GA, Santos RC, Seville J, Al-Duri B, Lee CKY, Holmes ABet al., 2004, Solubilities of p-tolylboronic acid, bromobenzene, and 4-phenyltoluene in carbon dioxide at elevated pressures, Journal of Chemical and Engineering Data, Vol: 49, Pages: 48-52, ISSN: 0021-9568

Solubility data were determined for the first time for p-tolylboronic acid, bromobenzene, and 4-phenyl-toluene in carbon dioxide at (353 and 383) K and between pressures of (98 and 317) bar. Data were obtained using a cloud point apparatus fitted with an internal stirrer. The results were correlated using Chrastil's density based model.

Journal article

Mak CSK, Evans NR, Watkins SE, Williams CK, Holmes AB, Boothby CE, Köhler A, Friend RHet al., 2004, Singlet and triplet emission from polymers for OLED applications, 8th Conference on Organic Light-Emitting Materials and Devices, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, Pages: 24-34, ISSN: 0277-786X

Conference paper

Haque SA, Palomares E, Xu CG, Potter RJ, Holmes AB, Durrant JRet al., 2004, Slow charge recombination at a dye sensitized nanocrystalline TiO2/organic semiconductor heterojunction employing Al2O3 coatings, Bellingham, Conference on Organic Photovoltaics IV, San Diego, CA, 2003, Publisher: SpIE -International Society Optical Engineering, Pages: 9-15

Conference paper

Haque SA, Palomares E, Xu CG, Potter RJ, Holmes AB, Durrant JRet al., 2004, Slow charge recombination at a dye sensitized nanocrystalline TiO2/organic semiconductor heterojunction employing Al2O3 coatings, Bellingham, Conference on Organic Photovoltaics IV, San Diego, CA, 2003, Publisher: SpIE -International Society Optical Engineering, Pages: 9-15

Conference paper

Haque SA, Palomares E, Upadhyaya HM, Otley L, Potter RJ, Holmes AB, Durrant JRet al., 2003, Flexible dye sensitised nanocrystalline semiconductor solar cells, CHEMICAL COMMUNICATIONS, Pages: 3008-3009, ISSN: 1359-7345

Journal article

Samways DSK, Li W-H, Conway SJ, Holmes AB, Bootman MD, Henderson Get al., 2003, Co-incident signalling between mu-opioid and M3 muscarinic receptors at the level of Ca2+ release from intracellular stores: lack of evidence for Ins(1,4,5)P3 receptor sensitization., Biochem J, Vol: 375, Pages: 713-720

Activation of G(i)/G(o)-coupled opioid receptors increases [Ca2+]i (intracellular free-Ca2+ concentration), but only if there is concomitant G(q)-coupled receptor activation. This G(i)/G(o)-coupled receptor-mediated [Ca2+]i increase does not appear to result from further production of Ins P3 [Ins(1,4,5) P3] in SH-SY5Y cells. In the present study, fast-scanning confocal microscopy revealed that activation of mu-opioid receptors alone by 1 muM DAMGO ([L-Ala, NMe-Phe, Gly-ol]-enkephalin) did not stimulate the Ins P3-dependent elementary Ca2+-signalling events (Ca2+ puffs), whereas DAMGO did evoke Ca2+ puffs when applied during concomitant activation of M3 muscarinic receptors with 1 muM carbachol. We next determined whether mu-opioid receptor activation might increase [Ca2+]i by sensitizing the Ins P3 receptor to Ins P3. DAMGO did not potentiate the amplitude of the [Ca2+]i increase evoked by flash photolysis of the caged Ins P3 receptor agonist, caged 2,3-isopropylidene-Ins P3, whereas the Ins P3 receptor sensitizing agent, thimerosal (10 muM), did potentiate this response. DAMGO also did not prolong the rate of decay of the increase in [Ca2+]i evoked by flash photolysis of caged 2,3-isopropylidene-Ins P3. Furthermore, DAMGO did not increase [Ca2+]i in the presence of the cell-membrane-permeable Ins P3 receptor agonist, Ins P3 hexakis(butyryloxymethyl) ester. Therefore it appears that mu-opioid receptors do not increase [Ca2+]i through either Ins P3 receptor sensitization, enhancing the releasable pool of Ca2+ or inhibition of Ca2+ removal from the cytoplasm.

Journal article

Peppiatt CM, Collins TJ, Mackenzie L, Conway SJ, Holmes AB, Bootman MD, Berridge MJ, Seo JT, Roderick HLet al., 2003, 2-Aminoethoxydiphenyl borate (2-APB) antagonises inositol 1,4,5-trisphosphate-induced calcium release, inhibits calcium pumps and has a use-dependent and slowly reversible action on store-operated calcium entry channels., Cell Calcium, Vol: 34, Pages: 97-108, ISSN: 0143-4160

The action of 2-aminoethoxydiphenyl borate (2-APB) on Ca(2+) signalling in HeLa cells and cardiac myocytes was investigated. Consistent with other studies, we found that superfusion of cells with 2-APB rapidly inhibited inositol 1,4,5-trisphosphate (InsP(3))-mediated Ca(2+) release and store-operated Ca(2+) entry (SOC). In addition to abrogating hormone-evoked Ca(2+) responses, 2-APB could antagonise Ca(2+) signals evoked by a membrane permeant InsP(3) ester. 2-APB also slowed the recovery of intracellular Ca(2+) signals consistent with an effect on Ca(2+) ATPases. The inhibitory action of 2-APB on InsP(3) receptors (InsP(3)Rs), SOC channels and Ca(2+) pumps persisted for several minutes after washout of the compound. Application of 2-APB to unstimulated cells had no effect on subsequent Ca(2+) responses suggesting that it has a use-dependent action. Mitochondria in cells treated with 2-APB showed a rapid and slowly reversible swelling. 2-APB did not cause the mitochondria to depolarise, but it reduced the extent of mitochondrial calcium uptake. Although 2-APB has been demonstrated not to affect voltage-operated Ca(2+) channels or ryanodine receptors, we found that it gave a concentration-dependent long-lasting inhibition of Ca(2+) signalling in electrically-stimulated cardiac myocytes, where InsP(3)Rs and SOC channels do not play a significant role. Our data suggest that 2-APB has multiple cellular targets, a use-dependent action, is difficult to reverse and may affect Ca(2+) signalling in cell types where InsP(3) and SOC are not active.

Journal article

Luscombe CK, Huck WTS, Holmes AB, Lu T, Leeke GA, Santos RCD, Al-Duri B, Seville JPKet al., 2003, Patterned deposition from compressed carbon dioxide, Pages: 103-108, ISSN: 0272-9172

Compressed CO2 is employed as the solvent for the deposition of polymers onto patterned surfaces created by a lithographic technique. This deposition technique should have wide applicability in the deposition of organic and polymeric materials for optoelectronic devices. The advantage of controlled deposition confers a further benefit in the control of the patterned surface. In a specific example a perfluorinated polymer was dissolved in liquid carbon dioxide. The polymer solution was deposited by use of a nozzle onto a pre-patterned surface. The resulting polymer film showed a clear image of the original pattern as measured by optical microscopy.

Conference paper

Luscombe CK, Li HW, Huck WTS, Holmes ABet al., 2003, Fluorinated silane self-assembled monolayers as resists for patterning indium tin oxide, Langmuir, Vol: 19, Pages: 5273-5278, ISSN: 0743-7463

We report the formation of self-assembled monolayers (SAMs) on indium tin oxide (ITO) substrates with perfluoroorganosilanes in liquid and supercritical carbon dioxide and a method of patterning the monolayer that does not use any organic solvents. The monolayers formed were used as an etch resistant during the formation of patterns as small as 300 nm. The monolayers were characterized using wettability experiments, surface FT-IR, cyclic voltammetry, and AFM. The effects of temperature and adsorption time on the formation of SAMs were explored. Advancing contact angles as high as 105° and fractional surface coverages up to 0.96 were achieved by exposing the ITO surfaces to silanes in scCO2 for 15 h. Surface FT-IR results show peaks at 1212 and 1152 cm-1, typical for disordered monolayers. Yet, these SAMs are resistant to wet etching for over 10 h, indicating that dense carbon dioxide is a superior solvent for SAM formation of perfluorosilanes on ITO.

Journal article

Berst F, Holmes AB, Ladlow M, 2003, The development and preparation of the 2,4-dimethoxybenzyl arylhydrazine (DMBAH) "latent" safety-catch linker: solid phase synthesis of ketopiperazines., Org Biomol Chem, Vol: 1, Pages: 1711-1719, ISSN: 1477-0520

The development and preparation of the 2,4-dimethoxybenzyl arylhydrazine (DMBAH) linker 3, a new class of "latent" safety-catch linker which is stable under Mitsunobu alkylation conditions and in the presence of amines and hydrazine, is reported. The utility of the new linker is exemplified by the synthesis of ketopiperazines (MKPs) 24 bearing up to four points of diversity using a cyclitive cleavage approach.

Journal article

Holmes AB, Park T, Schulte N, Haque SA, Durrant JH, Otley L, Potter RJ, Im C, Baessler Het al., 2003, New conjugated hole transport materials for solar cells, 225th National Meeting of the American-Chemical-Society, Publisher: AMER CHEMICAL SOC, Pages: U387-U387, ISSN: 0065-7727

Conference paper

Holmes A, 2003, Electronics - Polymers light the way, NATURE, Vol: 421, Pages: 800-801, ISSN: 0028-0836

Journal article

Pratt FL, Blundell SJ, Marshall IM, Lancaster T, Husmann A, Steer C, Hayes W, Fischmeister C, Martin RE, Holmes ABet al., 2003, μSR in polymers, Physica B: Condensed Matter, Vol: 326, Pages: 34-40, ISSN: 0921-4526

μSR can be applied to the study of various dynamical processes in polymers. These processes may relate to carrier motion, as in studies of conducting polymers which make use of muon generated polarons to measure carrier diffusion rates. Alternatively the processes of interest may be related to the structural dynamics of the polymer, which can show dramatic changes around the glass transition temperature. We report here examples of the use of μSR to study the muon states and muon mobility in the polymers polyethylene and polytetrafluoroethylene, where coherent FμF precession signals have been observed. In the case of polystyrene, muon radical states formed on the phenyl ring have been used to make a detailed study of the dynamical freezing and onset of static disorder that accompanies the glass transition. Finally, we report a study of polaron diffusion in two polyphenylenevinylene conducting polymers. © 2002 Elsevier Science B.V. All rights reserved.

Journal article

Haque SA, Park T, Holmes AB, Durrant JRet al., 2003, Transient optical studies of interfacial energetic disorder at nanostructured dye-sensitised inorganic/organic semiconductor heterojunctions, CHEMPHYSCHEM, Vol: 4, Pages: 89-+, ISSN: 1439-4235

Journal article

Kopecky DJ, Rychnovsky SD, Péron GLN, Fischmeister CRN, Holmes ABet al., 2003, Preparation of -acetoxy ethers by the reductive acetylation of esters: Endo-1-bornyloxyethyl acetate: [(Ethanol, 1-[[(1r,2s,4r)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]oxy]-, acetate)], Organic Syntheses, Vol: 80, ISSN: 0078-6209

Journal article

Nelson TD, Rosen JD, Bhupathy M, McNamara J, Sowa MJ, Rush C, Crocker LS, Conway SJ, Holmes ABet al., 2003, Tetrabenzyl pyrophosphate: [[Diphosphoric acid, tetrakis(phenylmethyl) ester]], Organic Syntheses, Vol: 80, Pages: 219-226, ISSN: 0078-6209

Journal article

Ferguson ML, O'Leary DJ, Grubbs RH, Stamp LM, Holmes ABet al., 2003, Ring-closing metathesis synthesis of N-Boc-3-pyrroline: [(1H-pyrrole-1-carboxylic acid, 2,5-dihydro-, 1,1-dimethylethyl ester)], Organic Syntheses, Vol: 80, Pages: 85-92, ISSN: 0078-6209

Journal article

Iserloh U, Oderaotoshi Y, Kanemasa S, Curran DP, Gordon RS, Holmes ABet al., 2003, Synthesis of (R,R)-4,6-dibenzofurandiyl-2,2'-bis (4-phenyloxazoline) (DBFOX/PH) – A novel tridentate ligand: [[oxazole, 2,2'-(4,6-dibenzofurandiyl)bis(4,5-dihydro-4-phenyl-, (4R,4'R)-]], Organic Syntheses, Vol: 80, Pages: 46-56, ISSN: 0078-6209

Journal article

Park T, Haque SA, Potter RJ, Holmes AB, Durrant JRet al., 2003, A supramolecular approach to lithium ion solvation at nanostructured dye sensitised inorganic/organic heterojunctions, CHEMICAL COMMUNICATIONS, Pages: 2878-2879, ISSN: 1359-7345

Journal article

Blundell SJ, Pratt FL, Marshall IM, Steer CA, Hayes W, Husmann A, Fischmeister C, Martin RE, Holmes ABet al., 2002, Muon-spin relaxation study of anisotropic charge carrier motion in polyphenylene vinylene-based polymers, Journal of Physics Condensed Matter, Vol: 14, Pages: 9987-9995, ISSN: 0953-8984

Muon-spin relaxation (μSR) experiments on the conducting polymers poly(2, 3-dibutoxy-1, 4-phenylene vinylene) and poly(2, 5-bis(dimethyloctylsilyl)-1, 4-phenylene vinylene) probe the dynamics of the highly mobile polarons created by the muon-implantation process in which muonium reacts with the polymer forming a radical state. The fluctuating spin density induced by the electronic spin defect rapidly diffusing up and down the chain leads to a characteristic relaxation, the temperature and field dependences of which permit the extraction of intrachain and interchain diffusion rates. The intrachain diffusion rate decreases with temperature and can be fitted to a model of phonon-limited transport. The interchain diffusion rate increases with temperature and can be fitted to an activated temperature dependence.

Journal article

Johenning FW, Zochowski M, Conway SJ, Holmes AB, Koulen P, Ehrlich BEet al., 2002, Distinct intracellular calcium transients in neurites and somata integrate neuronal signals., J Neurosci, Vol: 22, Pages: 5344-5353

Intracellular calcium signals have distinct temporal and spatial patterns in neurons in which signal initiation and repetitive spiking occurs predominantly in the neurite. We investigated the functional implications of the coexpression of different isoforms of ryanodine receptors (RyR) and inositol 1,4,5-trisphosphate receptors (InsP3Rs) using immunocytochemistry, Western blotting, and calcium imaging in neuronally differentiated PC12 cells. InsP3R type III, an isoform that has been shown to be upregulated in neuronal apoptosis, is exclusively expressed in the soma, serving as a gatekeeper for high-magnitude calcium surges. InsP3R type I is expressed throughout the cell and can be related to signal initiation and repetitive spiking in the neurite. RyR types 2 and 3 are distributed throughout the cell. In the soma, they serve as amplifying molecular switches, facilitating recruitment of the InsP3R type III-dependent pool. In the neurite, they decrease the probability of repetitive spiking. Use of a cell-permeant analog of InsP3 suggested that regional specificity in InsP3 production and surface-to-volume effects play minor roles in determining temporal and spatial calcium signaling patterns in neurons. Our findings suggest that additional modulatory processes acting on the intracellular channels are necessary to generate spatially specific calcium signaling.

Journal article

Smith CJ, Holmes AB, Press NJ, 2002, The total synthesis of alkaloids (-)-histrionicotoxin 259A, 285C and 285E., Chem Commun (Camb), Pages: 1214-1215, ISSN: 1359-7345

The first total syntheses of three "unsymmetrical" (i.e. different terminal groups in the side chains) members of the histrionicotoxin family of alkaloids have been accomplished via stepwise introduction of the two side chain moieties onto a common tricyclic core.

Journal article

Mackenzie L, Bootman MD, Laine M, Berridge MJ, Thuring J, Holmes A, Li WH, Lipp Pet al., 2002, The role of inositol 1,4,5-trisphosphate receptors in Ca<SUP>2+</SUP> signalling and the generation of arrhythmias in rat atrial myocytes, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 541, Pages: 395-409, ISSN: 0022-3751

Journal article

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