@article {2628,
	title = {Glycosylated tetrahydrosalens as multifunctional molecules for Alzheimer{\textquoteright}s therapy},
	journal = {Dalton Transactions},
	number = {16},
	year = {2009},
	note = {ISI Document Delivery No.: 430GYTimes Cited: 8Cited Reference Count: 65Storr, Tim Scott, Lauren E. Bowen, Meryn L. Green, David E. Thompson, Katherine H. Schugar, Harvey J. Orvig, Chris},
	pages = {3034-3043},
	type = {Article},
	abstract = {The tetrahydrosalens N,N{\textquoteright}-bis(2-hydroxybenzyl)-ethane-1,2-diamine (H2L1), N, N{\textquoteright}-bis(2-hydroxybenzyl)-(-)-1,2-cyclohexane-(1R, 2R)-diamine (H2L2), N,N{\textquoteright}-bis(2-hydroxybenzyl)-N,N{\textquoteright}-dimethyl-ethane-1,2-diamine (H2L3), N,N{\textquoteright}-bis(2-hydroxybenzyl)-N,N{\textquoteright}-dibenzyl-ethane-1,2diamine (H2L4), and N,N{\textquoteright}-bis(2-(4-tert-butyl) hydroxybenzyl)-ethane-1,2-diamine (H2L5), as well as their prodrug glycosylated forms, GL(1-5), have been prepared and evaluated in vitro for their potential use as Alzheimer{\textquoteright}s disease (AD) therapeutics. Dysfunctional interactions of metal ions, especially those of Cu, Zn, and Fe, with the amyloid-beta (A beta) peptide are hypothesised to play an important role in the aetiology of AD, and disruption of these aberrant metal-peptide interactions via chelation therapy holds considerable promise as a therapeutic strategy. Tetrahydrosalens such as H2L1-5 have a significant affinity for metal ions, and thus should be able to compete with the A beta peptide for Cu, Zn, and Fe in the brain. This activity was assayed in vitro via a turbidity assay; H2L1 and H2L3 were found to attenuate A beta(1-40) aggregation after exposure to Cu2+ and Zn2+. In addition, H2L1-5 were determined to be potent antioxidants on the basis of an in vitro antioxidant assay. GL(1-5) were prepared as metal binding prodrugs; glycosylation is intended to prevent systemic metal binding, improve solubility, and enhance brain uptake. Enzymatic (beta-glucosidase) deprotection of the carbohydrate moieties was facile, with the exception of GL(4), demonstrating the general feasibility of this prodrug approach. Finally, a representative prodrug, GL(3), was determined to be non-toxic over a large concentration range in a cell viability assay.},
	keywords = {A-BETA, ACTIVITY, antioxidant, COMPLEXES, DISEASE, HYDROGEN-PEROXIDE, IN-VITRO, NEURODEGENERATIVE DISORDERS, OXIDATIVE STRESS, TRANSGENIC MICE, zinc},
	isbn = {1477-9226},
	url = {<Go to ISI>://000264978300018},
	author = {Storr, T. and Scott, L. E. and Bowen, M. L. and Green, D. E. and Thompson, K. H. and Schugar, H. J. and Orvig, Chris}
}
@article {5226,
	title = {Reaction of human myoglobin and peroxynitrite: Characterizing biomarkers for myoglobin-derived oxidative stress},
	journal = {Biochemical and Biophysical Research Communications},
	volume = {286},
	number = {2},
	year = {2001},
	note = {ISI Document Delivery No.: 465TNTimes Cited: 11Cited Reference Count: 32},
	month = {Aug},
	pages = {352-356},
	type = {Article},
	abstract = {Mixtures of human myoglobin (Mb) (or the Y103F variant of human Mb), authentic peroxynitrite (ONOO-, ONOO-:protein 2 mol/mol), and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) gave radicals adducts at cysteine-110 (DMPO-C110) that are detected directly by electron paramagnetic magnetic spectroscopy (EPR). DMPO-C110 was detected exclusively over a range of DMPO concentrations (DMPO:protein ratios 25-100 mol/mol). Treatment of human Mb (or Y103F Mb) with the ONOO- generator 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium (SIN-1) chloride (ONOO-: protein 5 mol/mol) yielded a cross-linked Mb dimer as judged by SDS-PAGE analyses. Addition of DMPO or carbonate effectively eliminated the cross-linked product. Mass analyses of samples containing human Mb (or Y103F Mb), carbonate, and ONOO- indicated that nitration occurs exclusively at Y103. Thus, reaction of human Mb and ONOO- yields specific products that depend on the presence or absence of physiological concentrations of carbonate. These products may serve as biomarkers for the participation of Mb-derived radicals in the oxidative damage associated with myocardial reperfusion injury. (C) 2001 Academic Press.},
	keywords = {ARRHYTHMIAS, free radical, GENERATION, HYDROGEN-PEROXIDE, ischaemia reperfusion injury, MECHANISMS, MYOGLOBIN, NITRATION, NITRIC-OXIDE, nitro-tyrosine, peroxynitrite, protein-thiyl radical, radicals, REPERFUSION INJURY, SITE-DIRECTED MUTAGENESIS, SUPEROXIDE, SYSTEMS},
	isbn = {0006-291X},
	url = {<Go to ISI>://000170606200020},
	author = {Witting, P. K. and Mauk, A. G. and Douglas, D. J. and Stocker, R.}
}
@article {4978,
	title = {Reaction of human myoglobin and H2O2 - Involvement of a thiyl radical produced at cysteine 110},
	journal = {Journal of Biological Chemistry},
	volume = {275},
	number = {27},
	year = {2000},
	note = {ISI Document Delivery No.: 332QGTimes Cited: 55Cited Reference Count: 52},
	month = {Jul},
	pages = {20391-20398},
	type = {Article},
	abstract = {The human myoglobin (Mb) sequence is similar to other mammalian Mb sequences, except for a unique cysteine at position 110. Reaction of wild-type recombinant human Mb, the C110A variant of human Mb, or horse heart Mb with H2O2 (protein/H2O2 = 1:1.2 mol/mol) resulted in formation of tryptophan peroxyl (Trp-OO.) and tyrosine phenoxyl radicals as detected by EPR spectroscopy at 77 K. For wild-type human Mb, a second radical (g similar to 2.036) was detected after decay of Trp-OO. that was not observed for the C110A variant or horse heart Mb. When the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) was included in the reaction mixture at protein/DMPO ratios less than or equal to 1:10 mol/mol, a DMPO adduct exhibiting broad absorptions was detected. Hyperfine couplings of this radical indicated a DMPO-thiyl radical. Incubation of mild-type human Mb with thiol-blocking reagents prior to reaction with peroxide inhibited DMPO adduct formation, whereas at protein/DMPO ratios greater than or equal to 1:25 mol/mol, DMPO-tyrosyl radical adducts were detected. Mass spectrometry of wild-type human Mb following reaction with H2O2 demonstrated the formation of a homodimer (mass of 34,107 +/- 5 atomic mass units) sensitive to reducing conditions. The human Mb C110A variant afforded no dimer under identical conditions. Together, these data indicate that reaction of wild-type human Mb and H2O2 differs from the corresponding reaction of other myoglobin species by formation of thiyl radicals that lead to a homodimer through intermolecular disulfide bond formation.},
	keywords = {ASCORBATE, CROSS-LINKING, enzyme catalysis, HEMOGLOBIN, HYDROGEN-PEROXIDE, LOW-DENSITY-LIPOPROTEIN, METMYOGLOBIN, OXIDATION, SPERM WHALE MYOGLOBIN, SPIN ADDUCTS},
	isbn = {0021-9258},
	url = {<Go to ISI>://000088084500025},
	author = {Witting, P. K. and Douglas, D. J. and Mauk, A. G.}
}
@article {3944,
	title = {Polyhaloporphyrins: Unusual ligands for metals and metal-catalyzed oxidations},
	journal = {Accounts of Chemical Research},
	volume = {30},
	number = {6},
	year = {1997},
	note = {ISI Document Delivery No.: XE058Times Cited: 283Cited Reference Count: 63},
	month = {Jun},
	pages = {251-259},
	type = {Review},
	keywords = {halogenated porphyrins, HYDROGEN-PEROXIDE, HYDROXYLATION, Iron(III), IRON-PORPHYRIN COMPLEXES, manganese porphyrins, METALLOPORPHYRINS, MODEL SYSTEMS, porphyrins, SATURATED-HYDROCARBONS, TERT-BUTYL HYDROPEROXIDE},
	isbn = {0001-4842},
	url = {<Go to ISI>://A1997XE05800004},
	author = {Dolphin, D. and Traylor, T. G. and Xie, L. Y.}
}
@article {3777,
	title = {A biomimetic study of cytochrome P450 related oxidations of toluenes using synthetic hemin},
	journal = {Bulletin of the Chemical Society of Japan},
	volume = {69},
	number = {12},
	year = {1996},
	note = {ISI Document Delivery No.: WB844Times Cited: 6Cited Reference Count: 68},
	month = {Dec},
	pages = {3513-3521},
	type = {Article},
	abstract = {A mechanistic study of the oxidation of toluene and its derivatives in a model system designed to mimic cytochrome P450 (P450) using iron tetrakis(2,6-dichlorophenyl)porphyrin chloride (FeTPPC8Cl) and pentafluoroiodosylbenzene (PFIB:C(6)F(5)lO) in dichloromethane is reported. The oxidation products were the corresponding benzyl alcohols and aldehydes; no further oxidation products were observed. The relative reaction rates were obtained in competitive reactions including the use of deuterated analogues. In the present model system, Hammett plots and isotope effects indicated conclusively that the rate-determining step was a hydrogen atom abstraction to the oxoiron intermediate which was then followed by a rebound of an OH group. The concerted mechanism and the rebound mechanism were discussed in terms of the differences in reactivities between the model system and natural P450 enzymes and similar monooxygenation enzymes.},
	keywords = {ALIPHATIC, AROMATIC-COMPOUNDS, CRYSTAL-STRUCTURE, DEPENDENT MONO-OXYGENASES, HYDROGEN-PEROXIDE, HYDROXYLATION, INDUCED, IRON(III) PORPHYRINS, LIVER MICROSOMAL CYTOCHROME-P-450, METABOLISM, MODEL SYSTEMS, RAT-LIVER},
	isbn = {0009-2673},
	url = {<Go to ISI>://A1996WB84400017},
	author = {Nakano, T. and Agatsuma, N. and Kodama, S. and Kakuda, H. and Dolphin, D.}
}
