@article {2396,
	title = {Binding and Uptake of RGD-Containing Ligands to Cellular alpha(v)beta(3) Integrins},
	journal = {International Journal of Peptide Research and Therapeutics},
	volume = {15},
	number = {1},
	year = {2009},
	note = {ISI Document Delivery No.: 430WTTimes Cited: 2Cited Reference Count: 34Cressman, Sonya Sun, Ying Maxwell, E. Jane Fang, Ning Chen, David D. Y. Cullis, Pieter R.},
	month = {Mar},
	pages = {49-59},
	type = {Article},
	abstract = {The cyclic peptide, cRGDf[N(me)]V, binds to the alpha(v)beta(3) integrin and can disrupt binding of the integrin to its natural ligands in the extracellular matrix. In this work, the ability of a water-soluble, fluorescently labeled variant of the RGD-containing peptide (cRGDfK-488) to bind to integrins on human umbilical vascular endothelial cells (HUVEC) and subsequently undergo endocytosis was characterized. This information was compared to the binding and uptake properties of an alpha(v)beta(3) integrin-specific monoclonal antibody, LM609X. The specificity of the RGD-containing peptide is assessed by comparison with control peptide that does not bind to the alpha(v)beta(3) integrin, cRADfK-488. Using a high purity construct, it is shown that the RGD ligand exhibits dissociation constants in the micromolar range whereas LM609X exhibits dissociation constants in the nanomolar range. However, the RGD ligand showed greater uptake following incubation at temperatures which permit endocytosis. A 7.4-fold increase in uptake of the RGD peptide was observed following a 1 h incubation with HUVEC at 37 degrees C (an endocytosis permissive temperature), as compared to that at 4 degrees C (an endocytosis prohibitive temperature). In contrast, only a 1.9-fold increase in cell-associated fluorescence was observed for similar incubations with LM609X. Results from fluorescence microscopy supports the notion that the RGD peptide is rapidly endocytosed at 37 degrees C as compared to LM609X. These results are discussed with regard to previous work indicating that RGD ligands enter cells by integrin-independent pathways. These studies provide well-controlled measures of how RGD ligands stimulate endocytosis. This may be of considerable interest for intracellular delivery of ligand-associated drugs in anti-angiogenic applications.},
	keywords = {alpha(v)beta(3) integrins, ALPHA-V-BETA-3, ANGIOGENESIS, ANTAGONISTS, ANTITUMOR EFFICACY, CELLS, Endocytosis, EXPRESSION, IN-VIVO, PEPTIDES, RGD, TARGETED DRUG-DELIVERY, TUMOR VASCULATURE},
	isbn = {1573-3149},
	url = {<Go to ISI>://000265022900007},
	author = {Cressman, S. and Sun, Y. and Maxwell, E. J. and Fang, N. and Chen, D. D. Y. and Cullis, P. R.}
}
@article {2637,
	title = {Vanadium treatment of type 2 diabetes: A view to the future},
	journal = {Journal of Inorganic Biochemistry},
	volume = {103},
	number = {4},
	year = {2009},
	note = {ISI Document Delivery No.: 429EUTimes Cited: 20Cited Reference Count: 41Thompson, Katherine H. Lichter, Jay LeBel, Carl Scaife, Michael C. McNeill, John H. Orvig, Chris6th International Vanadium SymposiumJUL 17-19, 2008Lisbon, PORTUGALSp. Iss. SI},
	month = {Apr},
	pages = {554-558},
	type = {Proceedings Paper},
	abstract = {3-Hydroxy-2-methyl-4-pryone and 2-ethyl 3-hydroxy-4-pyrone (maltol and ethyl maltol, respectively) have proven especially suitable a ligands for vanadyl tons, fit potential insulin enhancing agents for diabetes mellitus. Both bis(maltolato)oxovanadium(IV) (BMOV), and the ethylmaltol analog, bis(ethylmaltolato)oxovanadium(IV) (BEOV), have the desired intermediate stability for pro-drug use, and have undergone extensive pie-clinical testing for safety and efficacy. Pharmacokinetic evaluation indicates a pattern of biodistribution consistent with fairly rapid dissociation and uptake, binding to serum transferrin for systemic circulation and transport to tissues, with preferential uptake in bone. These bis-ligand oxovanadium(IV) (VOL2) compounds have a clear advantage over inorganic vanadyl sulfate in terms of bioavailability and pharmaceutical efficacy. BEOV has now completed Phase I and has advanced to Phase II clinical trials. In the Phase I trial, a ran-e of doses horn 10 mg, to 90 mg BEOV, given orally to non-diabetic volunteers, resulted in no adverse effects, all biochemical parameters remained within normal limits. In the Phase IIa trial, BEOV (AKP-020). 20 mg, daily for 28 clays, per os, in seven type 2 diabetic Subjects, was associated with reductions in fasting blood and glucose and \%HbA1c; improved responses to oral glucose tolerance testing, versus, the observed worsening of diabetic symptoms in the two placebo controls. (C) 2009 Elsevier Inc. All rights reserved.},
	keywords = {BIODISTRIBUTION, bis(ethylmaltolato)oxovanadium(IV), BIS(MALTOLATO)OXOVANADIUM(IV), CHEMISTRY, Diabetes mellitus, IN-VIVO, INSULIN SENSITIVITY, MALTOL, METAL-COMPLEXES, RATS, SERUM, SKELETAL-MUSCLE, SULFATE, VANADIUM},
	isbn = {0162-0134},
	url = {<Go to ISI>://000264904400011},
	author = {Thompson, K. H. and Lichter, J. and Lebel, C. and Scaife, M. C. and McNeill, J. H. and Orvig, Chris}
}
@article {2118,
	title = {Unimolecular Micelles based on Hydrophobically Derivatized Hyperbranched Polyglycerols: Biodistribution Studies},
	journal = {Bioconjugate Chemistry},
	volume = {19},
	number = {11},
	year = {2008},
	note = {ISI Document Delivery No.: 373VOTimes Cited: 7Cited Reference Count: 31Kainthan, Rajesh Kumar Brooks, Donald E.},
	month = {Nov},
	pages = {2231-2238},
	type = {Article},
	abstract = {We recently reported the synthesis and testing of a new class of unimolecular micelles based on hyperbranched polyglycerols as second generation synthetic plasma expanders and as general drug delivery vehicles. A detailed biodistribution study of two derivatized hyperbranched polyglycerols of different molecular weights derivatized with hydrophobic groups and short poly(ethylene glycol) chains is reported in this article. In mice, these materials are nontoxic with circulation half-lives as high as 31 h, controllable by manipulating the molecular weight and the degree of PEG derivatization. Organ accumulation is low, presumably due to the "pegylation" effect. Thermal degradation and hydrolysis data suggest that these polymers are highly stable with a long shelf life, a major advantage for a pharmaceutical product. Degradation under acidic conditions has been observed for these polymers.},
	keywords = {ALBUMIN, BIOLOGICAL EVALUATION, DENDRIMERS, IMMUNOGENICITY, IN-VIVO, LIPOSOMES, MOLECULAR-WEIGHT, POLYETHYLENE-GLYCOL DEGRADATION, POLYMERS, STARCH},
	isbn = {1043-1802},
	url = {<Go to ISI>://000261001800018},
	author = {Kainthan, R. K. and Brooks, D. E.}
}
@article {1603,
	title = {The anti-invasive compound motuporamine C is a robust stimulator of neuronal growth cone collapse},
	journal = {Neuroscience},
	volume = {139},
	number = {4},
	year = {2006},
	note = {ISI Document Delivery No.: 044SBTimes Cited: 7Cited Reference Count: 41},
	pages = {1263-1274},
	type = {Article},
	abstract = {Neuronal outgrowth is a fundamental process for normal development of the nervous system. Despite recent advances, the molecular mechanisms governing neuronal motility are still poorly understood. To provide insight into the intracellular signaling mechanisms required for neuronal outgrowth, we have characterized the effects of a compound previously identified for its anti-motility effects on transformed cells. We show that this compound, motuporamine C, acts as a robust inhibitor of chick neurite outgrowth in a dose-dependent fashion. Furthermore, in the presence of motuporamine C, growth cone collapse is observed, followed by neurite retraction. After removal, growth cones re-extend lamellipodial and filopodial processes and re-establish motility. Neurons exposed to motuporamine C exhibit a significant upregulation of active Rho-GTP. Additionally, effector-blocking experiments using Rho and Rho-associated kinase inhibitors indicate that the Rho pathway plays a critical role in motuporamine C-mediated growth cone collapse. Thus, we have characterized a novel anti-motility compound that has a robust inhibitory effect on neuronal outgrowth and involves signaling through the Rho-Rho kinase collapse pathway. Due to these robust effects, motuporamine C may serve as a valuable tool in further examining the intracellular mechanisms associated with growth cone motility. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.},
	keywords = {ACTIN STRESS FIBERS, ADP-RIBOSYLATION, AXONAL GROWTH, BINDING PROTEIN-RHO, collapse, development, FOCAL ADHESIONS, growth cone, IN-VIVO, KINASE-ACTIVITY, LYSOPHOSPHATIDIC ACID, motuporamine, NEURITE RETRACTION, outgrowth, RECEPTORS, Rho GTPase},
	isbn = {0306-4522},
	url = {<Go to ISI>://000237691600009},
	author = {To, K. C. W. and Loh, K. T. and Roskelley, C. D. and Andersen, R. J. and O{\textquoteright}Connor, T. P.}
}
@article {1489,
	title = {Crystal structures of protein phosphatase-1 bound to motuporin and dihydromicrocystin-LA: Elucidation of the mechanism of enzyme inhibition by cyanobacterial toxins},
	journal = {Journal of Molecular Biology},
	volume = {356},
	number = {1},
	year = {2006},
	note = {ISI Document Delivery No.: 007AFTimes Cited: 17Cited Reference Count: 42},
	month = {Feb},
	pages = {111-120},
	type = {Article},
	abstract = {The microcystins and nodularins are tumour promoting hepatotoxins that are responsible for global adverse human health effects and wildlife fatalities in countries where drinking water supplies contain cyanobacteria. The toxins function by inhibiting broad specificity Ser/Thr protein phosphatases in the host cells, thereby disrupting signal transduction pathways. A previous crystal structure of a microcystin bound to the catalytic subunit of protein phosphatase-1 (PP-1c) showed distinct changes in the active site region when compared with protein phosphatase-1 structures bound to other toxins. We have elucidated the crystal structures of the cyanotoxins, motuporin (nodularin-V) and dihydromicrocystin-LA bound to human protein phosphatase-1c (gamma isoform). The atomic structures of these complexes reveal the structural basis for inhibition of protein phosphatases by these toxins. Comparisons of the structures of the cyanobacterial toxin:phosphatase complexes explain the biochemical mechanism by which microcystins but not nodularins permanently modify their protein phosphatase targets by covalent addition to an active site cysteine residue. (c) 2005 Elsevier Ltd. All rights reserved.},
	keywords = {CATALYTIC SUBUNIT, COMPLEX, crystal structure, cyanobacteria, IN-VIVO, microcystin, MICROCYSTIN-LR, MOLECULAR-MECHANISMS, nodularin, POTENT, PROGRAM, TUMOR-PROMOTER, TYPE-1},
	isbn = {0022-2836},
	url = {<Go to ISI>://000234938600010},
	author = {Maynes, J. T. and Luu, H. A. and Cherney, M. M. and Andersen, R. J. and Williams, D. and Holmes, C. F. B. and James, M. N. G.}
}
@article {1598,
	title = {Metal complexes of maltol and close analogues in medicinal inorganic chemistry},
	journal = {Chemical Society Reviews},
	volume = {35},
	number = {6},
	year = {2006},
	note = {ISI Document Delivery No.: 047UHTimes Cited: 43Cited Reference Count: 181},
	pages = {545-556},
	type = {Review},
	abstract = {The family of hydroxypyrones and close congeners, the hydroxypyridinones, is a particularly versatile class of ligands. The most widely investigated for medicinal applications are the 3-hydroxy-4-pyrones and the 1,2- 3,2- and 3,4-hydroxypyridinones. Key features of these ligands are: a six-membered ring, with a ring N or O atom either ortho or para to a ketone group, and two ortho exocyclic oxygen atoms. Readily functionalizable, the hydroxypyrones and hydroxypyridinones allow one to achieve a range of di- and trivalent metallocomplex stabilities and can include tissue or molecular targeting features by design. Research over the past several decades has greatly expanded the array of ligands that are the subject of this critical review. Ligand applications as diverse as iron removal or supplementation, contrast agents in imaging applications, and mobilization of undesirable excess metal ions will be surveyed herein.},
	keywords = {DIELS-ALDER REACTION, ENHANCED PFE(3+) VALUES, ETHYL MALTOL, evaluation, IN-VIVO, ION SEQUESTERING AGENTS, IRON-DEFICIENCY ANEMIA, MONOLAYERS, MRI CONTRAST AGENTS, ORAL, RAT SMALL-INTESTINE, SELF-ASSEMBLED, VANADYL SULFATE},
	isbn = {0306-0012},
	url = {<Go to ISI>://000237903700006},
	author = {Thompson, K. H. and Barta, C. A. and Orvig, Chris}
}
@article {1355,
	title = {Roles for the Drs2p-Cdc50p complex in protein transport and phosphatidylserine asymmetry of the yeast plasma membrane},
	journal = {Traffic},
	volume = {7},
	number = {11},
	year = {2006},
	note = {ISI Document Delivery No.: 093GOTimes Cited: 30Cited Reference Count: 76Chen, Sophie Wang, Jiyi Muthusamy, Baby-Periyanayaki Liu, Ke Zare, Sara Andersen, Raymond J. Graham, Todd R.},
	month = {Nov},
	pages = {1503-1517},
	type = {Article},
	abstract = {Drs2p, a P-type adenosine triphosphatase required for a phosphatidylserine (PS) flippase activity in the yeast trans Golgi network (TGN), was first implicated in protein trafficking by a screen for mutations synthetically lethal with arf1 (swa). Here, we show that SWA4 is allelic to CDC50, encoding a membrane protein previously shown to chaperone Drs2p from the endoplasmic reticulum to the Golgi complex. We find that cdc50 Delta exhibits the same clathrin-deficient phenotypes as drs2 Delta, including delayed transport of carboxypeptidase Y to the vacuole, mislocalization of resident TGN enzymes and the accumulation of aberrant membrane structures. These trafficking defects precede appearance of cell polarity defects in cdc50 Delta, suggesting that the latter are a secondary consequence of disrupting Golgi function. Involvement of Drs2p-Cdc50p in PS translocation suggests a role in restricting PS to the cytosolic leaflet of the Golgi and plasma membrane. Annexin V binding and papuamide B hypersensitivity indicate that drs2 Delta or cdc50 Delta causes a loss of plasma membrane PS asymmetry. However, clathrin and other endocytosis null mutants also exhibit a comparable loss of PS asymmetry, and studies with drs2-ts and clathrin (chc1-ts) conditional mutants suggest that loss of plasma membrane asymmetry is a secondary consequence of disrupting protein trafficking.},
	keywords = {annexin V, ATPase, B, CARBOXYPEPTIDASE-Y, Cdc50p, clathrin, CLATHRIN-COATED VESICLES, Drs2p, flippase, Golgi complex, GOLGI-COMPLEX, IN-VIVO, INTRAHEPATIC CHOLESTASIS, P-type, P-TYPE ATPASES, papuamide, phosphatidylserine, PHOSPHOLIPID, PUTATIVE AMINOPHOSPHOLIPID, SACCHAROMYCES-CEREVISIAE, TRANSLOCASES, TRANSLOCATION, VACUOLAR PROTEINS},
	isbn = {1398-9219},
	url = {<Go to ISI>://000241156500008},
	author = {Chen, S. and Wang, J. Y. and Muthusamy, B. P. and Liu, K. and Zare, S. and Andersen, R. J. and Graham, T. R.}
}
@article {1176,
	title = {New insights into the interactions of serum proteins with bis(maltolato)oxovanadium(IV): Transport and biotransformation of insulin-enhancing vanadium pharmaceuticals},
	journal = {Journal of the American Chemical Society},
	volume = {127},
	number = {14},
	year = {2005},
	note = {ISI Document Delivery No.: 914LQTimes Cited: 39Cited Reference Count: 66},
	month = {Apr},
	pages = {5104-5115},
	type = {Article},
	abstract = {Significant new insights into the interactions of the potent insulin-enhancing compound bis(maltolato)oxovanadium(IV) (BMOV) with the serum proteins, apo-transferrin and albumin, are presented. Identical reaction products are observed by electron paramagnetic resonance (EPR) with either BMOV or vanadyl sulfate (VOSO4) in solutions of human serum apo-transferrin. Further detailed study rules out the presence of a ternary ligand-vanadyl-transferrin complex proposed previously. By contrast, differences in reaction products are observed for the interactions of BMOV and VOSO4 with human serum albumin (HSA), wherein adduct formation between albumin and BMOV is detected. In BMOV-albumin solutions, vanadyl ions are bound in a unique manner not observed in comparable solutions Of VOSO4 and albumin. Presentation of chelated vanadyl ions precludes binding at the numerous nonspecific sites and produces a unique EPR spectrum which is assigned to a BMOV-HSA adduct. The adduct species cannot be produced, however, from a solution Of VOSO4 and HSA titrated with maltol. Addition of maltol to a VOSO4-HSA solution instead results in formation of a different end product which has been assigned as a ternary complex, VO(ma)(HSA). Furthermore, analysis of solution equilibria using a model system of BMOV with 1-methylimidazole (formation constant log K = 4.5(1), by difference electronic absorption spectroscopy) lends support to an adduct binding mode (VO(ma)(2)-HSA) proposed herein for BMOV and HSA. This detailed report of an in vitro reactivity difference between VOSO4 and BMOV may have bearing on the form of active vanadium metabolites delivered to target tissues. Albumin binding of vanadium chelates is seen to have a potentially dramatic effect on pharmacokinetics, transport, and efficacy of these antidiabetic chelates.},
	keywords = {BINDING CONSTANTS, COMPLEXES, DEPENDENT DIABETES-MELLITUS, ELECTRON-PARAMAGNETIC RESONANCE, HUMAN SEROTRANSFERRIN, IN-VIVO, IRON REMOVAL, METALLOKINETIC ANALYSIS, MIMETIC AGENT, TRANSFERRIN},
	isbn = {0002-7863},
	url = {<Go to ISI>://000228229600036},
	author = {Liboiron, B. D. and Thompson, K. H. and Hanson, G. R. and Lam, E. and Aebischer, N. and Orvig, Chris}
}
@article {1011,
	title = {Comparison of anti-hyperglycemic effect amongst vanadium, molybdenum and other metal maltol complexes},
	journal = {Journal of Inorganic Biochemistry},
	volume = {98},
	number = {5},
	year = {2004},
	note = {ISI Document Delivery No.: 824HVTimes Cited: 37Cited Reference Count: 7411th International Conference on Biological Inorganic ChemistryJUL 19-23, 2003Cairns, AUSTRALIA},
	month = {May},
	pages = {683-690},
	type = {Proceedings Paper},
	abstract = {A wide variety of vanadium-containing complexes have been tested, both in vivo and in vitro, as possible therapeutic agents for the oral treatment of type 2 diabetes mellitus. None so far has surpassed bis(maltolato)oxovanadium(IV) (BMOV) for glucose- and lipid-lowering in an orally available formulation. Ligand choice is clearly an important factor in pharmacological efficacy of vanadium compounds as insulin enhancing agents. In this study, we kept the ligand and dose the same, varying instead the metal ion bound to the maltolato ligand in a series of binary complexes of neutral charge. A requirement for vanadyl ion as the metal ion of choice was apparent; no other metal ion tested served as a suitable substitute. Amongst [MoO2](2+), Co(II), Cu(II), Cr(III), and Zn(II), only [MoO2](2+) and Co(II) showed any hypoglycemic activity at the ED50 dose for bis(maltolato)oxovanadium(IV), 0.6 mmol kg(-1) by oral gavage in streptozotocin (STZ)-diabetic rats within 72 It of administration of compound. (C) 2004 Elsevier Inc. All rights reserved.},
	keywords = {ABSORPTION, CHROMIUM, cobalt, COORDINATION MODE, copper, DEPENDENT DIABETES-MELLITUS, GLUCOSE-METABOLISM, IN-VIVO, INSULIN, LIPID-METABOLISM, MOLYBDENUM, RATS, VANADIUM, zinc, ZINC SUPPLEMENTATION},
	isbn = {0162-0134},
	url = {<Go to ISI>://000221678300004},
	author = {Thompson, K. H. and Chiles, J. and Yuen, V. G. and Tse, J. and McNeill, J. H. and Orvig, Chris}
}
@article {932,
	title = {Structural and dynamic independence of isopeptide-linked RanGAP1 and SUMO-1},
	journal = {Journal of Biological Chemistry},
	volume = {279},
	number = {47},
	year = {2004},
	note = {ISI Document Delivery No.: 870ZPTimes Cited: 14Cited Reference Count: 46},
	month = {Nov},
	pages = {49131-49137},
	type = {Article},
	abstract = {Although sumoylation regulates a diverse and growing number of recognized biological processes, the molecular mechanisms by which the covalent attachment of the ubiquitin-like protein SUMO can alter the properties of a target protein remain to be established. To address this question, we have used NMR spectroscopy to characterize the complex of mature SUMO-1 with the C-terminal domain of human RanGAP1. Based on amide chemical shift and N-15 relaxation measurements, we show that the C terminus of SUMO-1 and the loop containing the consensus sumoylation site in RanGAP1 are both conformationally flexible. Furthermore, the overall structure and backbone dynamics of each protein remain unchanged upon the covalent linkage of Lys(524) in RanGAP1 to the C-terminal Gly(97) of SUMO-1. Therefore, SUMO-1 and RanGAP1 behave as "beads-on-a-string," connected by a flexible isopeptide tether. Accordingly, the sumoylation-dependent interaction of RanGAP1 with the nucleoporin RanBP2 may arise through the bipartite recognition of both RanGAP1 and SUMO-1 rather than through a new binding surface induced in either individual protein upon their covalent linkage. We hypothesize that this conformational flexibility may be a general feature contributing to the recognition of ubiquitin-like modified proteins by their downstream effector machineries.},
	keywords = {BACKBONE DYNAMICS, BINDING, CONJUGATION, CRYSTAL-STRUCTURE, GTPASE-ACTIVATING PROTEIN, IN-VIVO, MOLYBDOPTERIN, NUCLEAR-PORE COMPLEX, SYNTHASE, UBC9, UBIQUITIN},
	isbn = {0021-9258},
	url = {<Go to ISI>://000225098100078},
	author = {Macauley, M. S. and Errington, W. J. and Okon, M. and Scharpf, M. and Mackereth, C. D. and Schulman, B. A. and McIntosh, L. P.}
}
@inbook {1012,
	title = {Vanadium compounds in the treatment of diabetes},
	booktitle = {Metal Ions in Biological Systems, Vol 41: Metal Ions and Their Complexes in Medication},
	series = {Metal Ions in Biological Systems},
	volume = {41},
	year = {2004},
	note = {ISI Document Delivery No.: BBZ13Times Cited: 38Cited Reference Count: 148Review270 MADISON AVE, NEW YORK, NY 10016 USA},
	pages = {221-252},
	publisher = {Marcel Dekker},
	organization = {Marcel Dekker},
	address = {New York},
	keywords = {ELECTRON-PARAMAGNETIC-RESONANCE, GLUCOSE-HOMEOSTASIS, IMPROVES GLYCEMIC CONTROL, IN-VIVO, INSULIN-RESISTANCE, ISOLATED, METALLOKINETIC ANALYSIS, OXYGEN-BRIDGED DIMER, PEROXOVANADIUM COMPOUNDS, PHOSPHOTYROSINE PHOSPHATASE INHIBITORS, RAT ADIPOCYTES},
	isbn = {0161-5149},
	url = {<Go to ISI>://000228348900007},
	author = {Thompson, K. H. and Orvig, Chris}
}
@article {642,
	title = {Anticancer agents from unique natural products sources},
	journal = {Pharmaceutical Biology},
	volume = {41},
	year = {2003},
	note = {ISI Document Delivery No.: 877RKTimes Cited: 5Cited Reference Count: 8344th Annual Meeting of the American-Society-of-PharmacognosyJUL 12-16, 2003Chapel Hill, NCAmer Soc PharmacognosySuppl. S},
	pages = {15-38},
	type = {Proceedings Paper},
	abstract = {The National Cooperative Natural Products Drug Discovery Group (NCNPDDG) "Anticancer Agents from Unique Natural Products Sources, CA 67786" was first awarded in September 1995. The goal of the project is to discover and develop novel anticancer agents from a variety of natural products sources. The key accomplishments of this NCDDG which will be highlighted in this manuscript include: Development of tools to probe fungi for the production of novel natural products by DNA-based probes. Discovery that the majority of these fungi can produce natural products via nonribosomal peptide synthetases, polyketide synthases, or both - a much larger percentage than current culturing techniques reveal. Identification of the MDR-selective cytotoxic agent austocystin D, and use of a novel yeast deletion strain approach to help identify its molecular target(s). Identification of hemiasterlin and other naturally occurring analogs as potent antimitotic agents with excellent in vivo activity against human solid tumors in mouse models. Development of a total synthesis of hemiasterlin. The utilization of this methodology to provide the first SAR for the hemiasterlin family of antimitotic agents and to identify the synthetic analog HTI-286, which is being examined in clinical trials as an anticancer agent. To provided technology transfer, educational opportunities and compensation to countries of origin for collection and study of their natural product resources. This NCNPDDG program has provided funding to research programs at the University of the Philippines, The University of the South Pacific in the Fiji Islands, Colombo University in Sri Lanka, the Instituto de Quimica de Sao Carlos, Universidade de Sao Paulo, Brazil, and the University of Papua New Guinea.},
	keywords = {ACTIVATED PROTEIN-KINASE, antitumor agents, austocystins, CYCLIN-DEPENDENT KINASES, CYTOTOXIC PEPTIDES, fungi, GROWTH-FACTOR RECEPTOR, hemiasterlins, IN-VIVO, LINKED-IMMUNOSORBENT-ASSAY, MARINE, MICROORGANISMS, MULTIDRUG-RESISTANCE, natural products, NCDDG, sponges, TRIPEPTIDE HEMIASTERLIN, TUMOR-CELL LINES, TYROSINE KINASE},
	isbn = {1388-0209},
	url = {<Go to ISI>://000225587500004},
	author = {Ireland, C. M. and Aalbersberg, W. and Andersen, R. J. and Ayral-Kaloustian, S. and Berlinck, R. G. S. and Bernan, V. and Carter, G. and Churchill, A. C. L. and Clardy, J. and Concepcion, G. P. and De Silva, E. D. and Discafani, C. and Fojo, T. and Frost, P. and Gibson, D. and Greenberger, L. M. and Greenstein, M. and Harper, M. K. and Mallon, R. and Loganzo, F. and Nunes, M. and Poruchynsky, M. S. and Zask, A.}
}
@article {784,
	title = {Chronic glucose-lowering effects of rosiglitazone and bis(ethylmaltolato)oxovanadium(IV) in ZDF rats},
	journal = {Canadian Journal of Physiology and Pharmacology},
	volume = {81},
	number = {11},
	year = {2003},
	note = {ISI Document Delivery No.: 749AHTimes Cited: 3Cited Reference Count: 47},
	month = {Nov},
	pages = {1049-1055},
	type = {Article},
	abstract = {The aim of this study was to determine if there was a synergistic or additive effect of a thiazolidinedione derivative (rosiglitazone (ROS)) and a vanadium compound (bis(ethylmaltolato)oxovanadium(IV) (BEOV)) on plasma glucose and insulin levels following chronic oral administration to Zucker diabetic fatty (ZDF) rats. Whole-blood vanadium levels were determined at time 0 and at days 1, 6, and 18. The doses of BEOV (0.1 mmol/kg) and ROS (2.8 mumol/kg) were selected to produce a glucose-lowering effect in 30\% (ED30) of animals. Both drugs were administered daily by oral gavage as suspensions in 1\% carboxymethylcellulose (CMC) in a volume of 2.5 mL/kg. The total volume administered to all rats was 5 mL/(kg-day). The combination of BEOV and ROS was effective in lowering plasma glucose levels to <9 mmol/L in 60\% of fatty animals as compared with 30\% for BEOV and 10\% for ROS alone. The age-dependent decrease in plasma insulin levels associated with \&beta;-cell failure in the ZDF rats did not occur in the BEOV-treated fatty groups. There was no effect of any treatment on body weight; however, there was a significant reduction in both food and fluid intake in fatty groups treated with BEOV. There were no overt signs of toxicity and no mortality in this study. Both BEOV and ROS were effective in lowering plasma glucose levels, as stated above, and there was at least an additive effect when BEOV and ROS were used in combination.},
	keywords = {ACTIVATED-RECEPTOR-GAMMA, bis(ethylmaltolato)oxovanadium(IV), diabetes, GLUT4, IN-VIVO, INSULIN SENSITIVITY, ORAL VANADYL, PHOSPHOENOLPYRUVATE-CARBOXYKINASE, RATS, rosigitazone, SKELETAL-MUSCLE, STREPTOZOTOCIN-DIABETIC RATS, TRANSLOCATION, VANADYL SULFATE, ZDF rats, ZUCKER FATTY},
	isbn = {0008-4212},
	url = {<Go to ISI>://000186896100007},
	author = {Yuen, V. G. and Bhanot, S. and Battell, M. L. and Orvig, Chris and McNeill, J. H.}
}
@article {4957,
	title = {Design of vanadium compounds as insulin enhancing agents},
	journal = {Journal of the Chemical Society-Dalton Transactions},
	number = {17},
	year = {2000},
	note = {ISI Document Delivery No.: 348MDTimes Cited: 77Cited Reference Count: 123},
	pages = {2885-2892},
	type = {Review},
	abstract = {Vanadium compounds, in vitro, stimulate glucose uptake and inhibit lipid breakdown, in a manner remarkably reminiscent of insulin{\textquoteright}s effects. In vivo, vanadium enhances insulin{\textquoteright}s plasma glucose and lipid-lowering properties, leading to normalization of diabetic symptoms in the presence of only minimal endogenous insulin. The coordination chemistry of vanadium has great versatility for adjustment of pharmacological characteristics. Vanadium compounds are generally also very redox active, which is both advantageous and detrimental for optimizing biochemical function. In this perspective, we review and comment on how these properties have been revealed, what questions have arisen along the way, and where future investigations may be headed. While this is not a comprehensive overview of all available compounds touted as {\textquoteright}insulin enhancing agents{\textquoteright}, it will focus on those which are distinctive in some way, or which are representative of the larger library of vanadium compounds, including all currently known relevant oxidation states of vanadium.},
	keywords = {AGENT, BIOLOGICAL-SYSTEMS, DEPENDENT DIABETES-MELLITUS, ECHO ENVELOPE, GLUCOSE-METABOLISM, IN-VIVO, MIMETIC, MODULATION, PEROXOVANADIUM COMPOUNDS, SKELETAL-MUSCLE, STREPTOZOTOCIN-TREATED RATS, TYROSINE PHOSPHORYLATION},
	isbn = {1470-479X},
	url = {<Go to ISI>://000088987800001},
	author = {Thompson, K. H. and Orvig, Chris}
}
@article {4683,
	title = {Vanadium compounds as insulin mimics},
	journal = {Chemical Reviews},
	volume = {99},
	number = {9},
	year = {1999},
	note = {ISI Document Delivery No.: 235XUTimes Cited: 376Cited Reference Count: 124},
	month = {Sep},
	pages = {2561-2571},
	type = {Review},
	keywords = {AGENT BIS(MALTOLATO)OXOVANADIUM(IV) BMOV, BIOLOGICAL-SYSTEMS, COMPOUNDS, GLUCOSE-METABOLISM, IN-VIVO, MIMETIC AGENT, OXIDATIVE STRESS, PEROXOVANADIUM, PHOSPHOTYROSINE PHOSPHATASE INHIBITORS, STREPTOZOTOCIN-DIABETIC RATS, TYROSINE PHOSPHORYLATION},
	isbn = {0009-2665},
	url = {<Go to ISI>://000082569800015},
	author = {Thompson, K. H. and McNeill, J. H. and Orvig, Chris}
}
@article {4168,
	title = {Effects of bis(maltolato)oxovanadium(IV) are distinct from food restriction in STZ-diabetic rats},
	journal = {American Journal of Physiology-Endocrinology and Metabolism},
	volume = {272},
	number = {1},
	year = {1997},
	note = {ISI Document Delivery No.: WG568Times Cited: 14Cited Reference Count: 39},
	month = {Jan},
	pages = {E30-E35},
	type = {Article},
	abstract = {In association with the insulin-mimetic properties, vanadium and related compounds have been shown to normalize hyperphagia associated with diabetes mellitus. The objective of this study was to clarify the effects of an organic vanadium compound, bis(maltolato)oxovanadium(IV) (BMOV), vs. food restriction on the metabolic abnormalities that occur in diabetes. BMOV was administered daily in drinking water to streptozotocin (STZ)-diabetic rats for 6 wk. Pair-fed groups were fed based on the intake for their respective counterparts from the previous day. Plasma parameters mere measured weekly after a carefully controlled 5-h fasting period. BMOV reduced plasma glucose (diabetic = 31.2 +/- 1.9, diabetic treated = 10.2 +/- 1.8, and diabetic pair fed = 34.2 +/- 1.1 mM), triglyceride, and cholesterol levels to normal without a concomitant increase in plasma insulin levels. There was no body weight gain in the diabetic pair-fed group compared with all other groups. BMOV but not pair feeding was effective in preventing the decreased cardiac function observed in STZ-diabetic rats. These data suggest that the glucose-lowering properties of BMOV are independent of the effects of dietary restriction and reinforce the efficacy of BMOV as an effective antihyperglycemic agent.},
	keywords = {diabetes, FA/FA, GLUCOSE-HOMEOSTASIS, glucose-lowering effect, HYPERINSULINEMIA, IN-VIVO, INSULIN SENSITIVITY, LONG-TERM IMPROVEMENT, MELLITUS, ORAL VANADATE, RATS, SPONTANEOUSLY HYPERTENSIVE RATS, STREPTOZOTOCIN, SULFATE, VANADYL},
	isbn = {0193-1849},
	url = {<Go to ISI>://A1997WG56800005},
	author = {Yuen, V. G. and Orvig, Chris and McNeill, J. H.}
}
@article {3927,
	title = {Tripodal aminophenolate ligand complexes of aluminum(III), gallium(III), and indium(III) in water},
	journal = {Inorganic Chemistry},
	volume = {36},
	number = {2},
	year = {1997},
	note = {ISI Document Delivery No.: WC887Times Cited: 34Cited Reference Count: 53},
	month = {Jan},
	pages = {236-248},
	type = {Article},
	abstract = {Four water-soluble amine phenols have been prepared: tris(((2-hydroxy-5-sulfobenzyl)amino)ethyl)amine (H(6)TRNS), 1,1,1-tris(((2-hydroxy-5-sulfobenzyl)amino)methyl)ethane (H(6)TAMS), 1,2,3-tris((2-hydroxy-5-sulfobenzyl)amino)propane (H(6)TAPS), and cis,cis-1,3,5-tris((2-hydroxy-5-sulfobenzyl)amino)cyclohexane (H(6)TACS). Complex formation constants have been measured at 25 degrees C (mu = 0.16 M NaCl): log K [M(TRNS)](3-) ([M(HTRNS)](2-)) M = Ga 28.55 (36.90), In 29.3 (34.9); log K [M(TAMS)](3-) ([M(HTAMS)](2-)) M = Al 22.5 (29.3), Ga 31.53, In 28.49; log K [M(TAPS)](3-) ([M(HTAPS)](2-)) M = Al 22.8 (29.0), Ga 31.54 (35.15), In 27.56 (31.93). The order of stability is Ga(III) > In(III) > Al(III) for H(6)TAMS and H(6)TAPS, while far H(6)TRNS it is Ga(III) approximate to In(lII) > Al(III). The solution structures of the complexes have been probed by multinuclear NMR (H-1, C-13, Al-27, Ga-71, In-115) and UV spectroscopic studies, and these solution structures are compared with solid state structures for analogous complexes. The H-1 NMR spectrum in D2O establishes TAPS to be preorganized for metal ion binding. H(6)TACS exists in the wrong conformation for metal ion binding, and this results in slow complexation kinetics and relatively weaker binding.},
	keywords = {ACID, BINDING, EQUILIBRIUM-CONSTANTS, GA(III), HUMAN-SERUM TRANSFERRIN, IN(III), IN-VIVO, METAL-IONS, SCHIFF-BASE LIGANDS, STABILITIES},
	isbn = {0020-1669},
	url = {<Go to ISI>://A1997WC88700021},
	author = {Caravan, P. and Orvig, Chris}
}
