Bruce P. Branchaud

University of Oregon, Eugene, Oregon, United States

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Publications (63)233.03 Total impact

  • Bruce P. Branchaud · G.-X. YU
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    ABSTRACT: The formation of monosaccharide cobaloximes and their cross coupling reactions with nitroalkyl anions are demonstrated to be useful in CC bond constructions to produce branched-chain monosaccharides.
    No preview · Article · Apr 2010 · ChemInform
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    ABSTRACT: Fatty acid nitration by nitric oxide-derived species yields electrophilic products that adduct protein thiols, inducing changes in protein function and distribution. Nitro-fatty acid adducts of protein and reduced glutathione (GSH) are detected in healthy human blood. Kinetic and mass spectrometric analyses reveal that nitroalkene derivatives of oleic acid (OA-NO2) and linoleic acid (LNO2) rapidly react with GSH and Cys via Michael addition reaction. Rates of OA-NO2 and LNO2 reaction with GSH, determined via stopped flow spectrophotometry, displayed second-order rate constants of 183 M(-1)S(-1) and 355 M(-1)S(-1), respectively, at pH 7.4 and 37 degrees C. These reaction rates are significantly greater than those for GSH reaction with hydrogen peroxide and non-nitrated electrophilic fatty acids including 8-iso-prostaglandin A2 and 15-deoxy-Delta(12,14)-prostaglandin J2. Increasing reaction pH from 7.4 to 8.9 enhanced apparent second-order rate constants for the thiol reaction with OA-NO2 and LNO2, showing dependence on the thiolate anion of GSH for reactivity. Rates of nitroalkene reaction with thiols decreased as the pKa of target thiols increased. Increasing concentrations of the detergent octyl-beta-d-glucopyranoside decreased rates of nitroalkene reaction with GSH, indicating that the organization of nitro-fatty acids into micellar or membrane structures can limit Michael reactivity with more polar nucleophilic targets. In aggregate, these results reveal that the reversible adduction of thiols by nitro-fatty acids is a mechanism for reversible post-translational regulation of protein function by nitro-fatty acids.
    Full-text · Article · Nov 2007 · Journal of Biological Chemistry
  • Bart J Dahl · Bruce P Branchaud
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    ABSTRACT: A bifunctional biaryl lactone has been synthesized that should be capable of iterative unidirectional aryl-aryl bond rotation via: (1) a diastereoselective lactone ring opening, (S)-1 to (P,S)-2 or (M,S)-2; (2) a chemoselective lactonization, (P,S)-2 or (M,S)-2 to (S)-3; and (3) a chemoselective hydrolysis, (S)-3 to (S)-1. Preliminary results of a racemic sample have indicated unidirectional 180 degrees rotation with very high directional selectivity per individual artificial molecular motor molecule through the first two steps of this sequence. [reaction: see text]
    No preview · Article · Jan 2007 · Organic Letters
  • Steven R Woodcock · Adam J V Marwitz · Paulo Bruno · Bruce P Branchaud
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    ABSTRACT: Unsaturated fatty acids are nitrated endogenously to produce nitrated lipids. Recent studies have shown that these nitrated lipids have high chemical reactivity and profound biological implications. We report an efficient, scalable synthesis which is regiospecific and stereoselective for all possible isomers of nitrated oleic acid: (E)- and (Z)-, 9- and 10-octadec-9-enoic acids.
    No preview · Article · Sep 2006 · Organic Letters
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    ABSTRACT: Nitric oxide ((*)NO)-derived reactive species nitrate unsaturated fatty acids, yielding nitroalkene derivatives, including the clinically abundant nitrated oleic and linoleic acids. The olefinic nitro group renders these derivatives electrophilic at the carbon beta to the nitro group, thus competent for Michael addition reactions with cysteine and histidine. By using chromatographic and mass spectrometric approaches, we characterized this reactivity by using in vitro reaction systems, and we demonstrated that nitroalkene-protein and GSH adducts are present in vivo under basal conditions in healthy human red cells. Nitro-linoleic acid (9-, 10-, 12-, and 13-nitro-9,12-octadecadienoic acids) (m/z 324.2) and nitro-oleic acid (9- and 10-nitro-9-octadecaenoic acids) (m/z 326.2) reacted with GSH (m/z 306.1), yielding adducts with m/z of 631.3 and 633.3, respectively. At physiological concentrations, nitroalkenes inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which contains a critical catalytic Cys (Cys-149). GAPDH inhibition displayed an IC(50) of approximately 3 microM for both nitroalkenes, an IC(50) equivalent to the potent thiol oxidant peroxynitrite (ONOO(-)) and an IC(50) 30-fold less than H(2)O(2), indicating that nitroalkenes are potent thiol-reactive species. Liquid chromatography-mass spectrometry analysis revealed covalent adducts between fatty acid nitroalkene derivatives and GAPDH, including at the catalytic Cys-149. Liquid chromatography-mass spectrometry-based proteomic analysis of human red cells confirmed that nitroalkenes readily undergo covalent, thiol-reversible post-translational modification of nucleophilic amino acids in GSH and GAPDH in vivo. The adduction of GAPDH and GSH by nitroalkenes significantly increased the hydrophobicity of these molecules, both inducing translocation to membranes and suggesting why these abundant derivatives had not been detected previously via traditional high pressure liquid chromatography analysis. The occurrence of these electrophilic nitroalkylation reactions in vivo indicates that this reversible post-translational protein modification represents a new pathway for redox regulation of enzyme function, cell signaling, and protein trafficking.
    Full-text · Article · Aug 2006 · Journal of Biological Chemistry
  • Kari A Trumbull · Bruce P Branchaud
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    ABSTRACT: A new radical-sensitive caging technique releases a caged molecule under lipid peroxidation conditions. In a competitive oxidation study with a model lipid, methyl linoleate, the oxidatively releasable xanthenyl caging groups is found to be 1.93+/-0.55 times more reactive than the lipid model compound.
    No preview · Article · Mar 2006 · Bioorganic & Medicinal Chemistry Letters
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    ABSTRACT: Mass spectrometric analysis of human plasma and urine revealed abundant nitrated derivatives of all principal unsaturated fatty acids. Nitrated palmitoleic, oleic, linoleic, linolenic, arachidonic and eicosapentaenoic acids were detected in concert with their nitrohydroxy derivatives. Two nitroalkene derivatives of the most prevalent fatty acid, oleic acid, were synthesized (9- and 10-nitro-9-cis-octadecenoic acid; OA-NO2), structurally characterized and determined to be identical to OA-NO2 found in plasma, red cells, and urine of healthy humans. These regioisomers of OA-NO2 were quantified in clinical samples using 13C isotope dilution. Plasma free and esterified OA-NO2 concentrations were 619 +/- 52 and 302 +/- 369 nm, respectively, and packed red blood cell free and esterified OA-NO2 was 59 +/- 11 and 155 +/- 65 nm. The OA-NO2 concentration of blood is approximately 50% greater than that of nitrated linoleic acid, with the combined free and esterified blood levels of these two fatty acid derivatives exceeding 1 microm. OA-NO2 is a potent ligand for peroxisome proliferator activated receptors at physiological concentrations. CV-1 cells co-transfected with the luciferase gene under peroxisome proliferator-activated receptor (PPAR) response element regulation, in concert with PPARgamma, PPARalpha, or PPARdelta expression plasmids, showed dose-dependent activation of all PPARs by OA-NO2. PPARgamma showed the greatest response, with significant activation at 100 nm, while PPARalpha and PPARdelta were activated at approximately 300 nm OA-NO2. OA-NO2 also induced PPAR gamma-dependent adipogenesis and deoxyglucose uptake in 3T3-L1 preadipocytes at a potency exceeding nitrolinoleic acid and rivaling synthetic thiazo-lidinediones. These data reveal that nitrated fatty acids comprise a class of nitric oxide-derived, receptor-dependent, cell signaling mediators that act within physiological concentration ranges.
    Full-text · Article · Jan 2006 · Journal of Biological Chemistry
  • Ying Lin · Bart J. Dahl · Bruce P. Branchaud
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    ABSTRACT: Net directed 180° bond rotation was achieved through diastereoselective ring-opening reactions in an achiral biaryl lactone using a chiral nucleophile followed by re-lactonization. The efficiency of the directed bond rotation has been determined by HPLC–MS to be 50% and 20% with two different chiral nucleophiles. These results demonstrate the potential for a prototype of a chemically driven synthetic molecular motor which has the advantages of both simplicity and flexibility in operation and is the first example of the use of a chiral auxiliary to induce transient axial chirality resulting in net directed bond rotation.
    No preview · Article · Nov 2005 · Tetrahedron Letters
  • Steven R. Woodcock · Bruce P. Branchaud
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    ABSTRACT: Ether tethers allow Heck cyclizations to proceed in high yields. Ester tethers lead to low yields. Styrene trapping experiments indicate that ester reactions form viable organopalladium intermediates that cannot cyclize efficiently.
    No preview · Article · Oct 2005 · Tetrahedron Letters
  • Andrew J. Robak · Bruce P. Branchaud
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    ABSTRACT: High-quality alloxazine (a flavin isomer) imprinted polymers have been made for the first time. A molecularly imprinted polymer (MIP) for the N1,N3-di-functionalized alloxazine template 2 was made. The MIP prepared for 2 exhibited excellent, highly selective molecular recognition for template 2, as determined by HPLC analysis using columns prepared with the MIP. This has also demonstrated that the core flavin structure can survive the imprinting process. (c) 2005 Elsevier Ltd. All rights reserved.
    No preview · Article · Aug 2005 · Tetrahedron Letters
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    ABSTRACT: The aqueous decay and concomitant release of nitric oxide (·NO) by nitrolinoleic acid (10-nitro-9,12-octadecadienoic acid and 12-nitro-9,12-octadecadienoic acid; LNO2) are reported. Mass spectrometric analysis of reaction products supports a modified Nef reaction as the mechanism accounting for the generation of ·NO by the aqueous reactions of fatty acid nitroalkene derivatives. Nitrolinoleic acid is stabilized by an aprotic milieu, with LNO2 decay and ·NO release strongly inhibited by phosphatidylcholine/cholesterol liposome membranes and detergents when present at levels above their critical micellar concentrations. The release of ·NO from LNO2 was induced by UV photolysis and triiodide-based ozone chemiluminescence reactions currently used to quantify putative protein nitrosothiol and N-nitrosamine derivatives. This reactivity of LNO2 complicates the qualitative and quantitative analysis of biological oxides of nitrogen when applying UV photolysis and triiodide-based analytical systems to biological preparations typically abundant in nitrated fatty acids. The results reveal that nitroalkene derivatives of linoleic acid are pluripotent signaling mediators that act not only via receptor-dependent mechanisms, but also by transducing the signaling actions of ·NO via pathways subject to regulation by the relative distribution of LNO2 to hydrophobic versus aqueous microenvironments.
    Full-text · Article · Jun 2005 · Journal of Biological Chemistry
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    ABSTRACT: Crystal structures of the tetrameric yellow-fluorescent protein zFP538 from the button polyp Zoanthus sp. and a green-emitting mutant (K66M) are presented. The atomic models have been refined at 2.7 and 2.5 A resolution, with final crystallographic R factors of 0.206 (R(free) = 0.255) and 0.190 (R(free) = 0.295), respectively, and have excellent stereochemistry. The fold of the protomer is very similar to that of green (GFP) and red (DsRed) fluorescent proteins; however, evidence from crystallography and mass spectrometry suggests that zFP538 contains a three-ring chromophore derived from that of GFP. The yellow-emitting species (lambda(em)(max) = 538 nm) is proposed to result from a transimination reaction in which a transiently appearing DsRed-like acylimine is attacked by the terminal amino group of lysine 66 to form a new six-membered ring, cleaving the polypeptide backbone at the 65-66 position. This extends the chromophore conjugation by an additional double bond compared to GFP, lowering the absorption and emission frequencies. Substitution of lysine 66 with aspartate or glutamate partially converts zFP538 into a red-fluorescent protein, providing additional support for an acylimine intermediate. The diverse and unexpected roles of the side chain at position 66 give new insight into the chemistry of chromophore maturation in the extended family of GFP-like proteins.
    No preview · Article · Feb 2005 · Biochemistry
  • Bart J. Dahl · Bruce P. Branchaud
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    ABSTRACT: A class of chiral biaryl molecules that have been designed to undergo unidirectional rotation about the aryl–aryl bond may show promise for future application in the area of synthetic molecular motors. These asymmetric molecules should be capable of channeling chemical energy into repeated 360° rotation in one direction. Herein we report the synthesis and characterization of one such biaryl molecule (1).
    No preview · Article · Dec 2004 · Tetrahedron Letters
  • Bruce P Branchaud · B Elizabeth Turner
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    ABSTRACT: Processing of trans-2-phenylcyclopropylmethanols 5 and 6 by the monocopper/tyrosine radical enzyme galactose oxidase led to mechanism-based inactivation with a partition ratio, (kcat + kinact)kinact, of approximately 1 and a primary deuterium isotope effect, kinact(H)kinact(D), of 3.2. The data are consistent with a radical mechanism for galactose oxidase with a short lived ketyl radical anion intermediate.
    No preview · Article · Feb 2002 · Methods in Enzymology
  • Bruce P Branchaud · Heather S Blanchette
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    ABSTRACT: Intermolecular additions of highly enantiomerically enriched episulfonium ions onto activated benzene rings are known to accomplish chiral Friedel–Crafts alkylations. Unactivated benzenes are either unreactive or can give low stereoselectivities. Intramolecular cyclizations should be faster than intermolecular additions; thus, cyclization reactions should be able to avoid undesired episulfonium ion racemization. The work reported here tests that hypothesis and demonstrates that cyclizations of enantiomerically enriched episulfonium ions onto unactivated benzene rings are highly stereoselective.
    No preview · Article · Jan 2002 · Tetrahedron Letters
  • G X Yu · David R. Tyler · Bruce P. Branchaud
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    ABSTRACT: Epimeric carbohydrate alkyl cobaloximes 4:5, 9:10, and 12:13 can be equilibrated thermally or photochemically. In each case, one isomer is strongly favored: exo-3-deoxy-3-pyridyldimethylglyoximatocobalt-1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose 4 for the 4:5 epimer pair, exo-3-deoxy-3-pyridyldimethylglyoximatocobalt-5-O-carboxymethyl-1,2-O-isopropylidene-alpha-D-xylofuranose 9 for the 9:10 epimer pair, and equatorial 1-deoxy-1-pyridyldimethylglyoximatocobalt-2,3,4,6-tetra-O-benzyl-beta-D-glucopyranose 12 for the 12:13 epimer pair. These data indicate that there is a strong facial preference for the coupling of py(dmgH)(2)Co(*) radicals with alkyl R(*) free radicals, with the preferred kinetic path leading to the more stable product.
    No preview · Article · Sep 2001 · The Journal of Organic Chemistry
  • Gregory K. Friestad · Bruce P. Branchaud
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    ABSTRACT: [16872-11-0] BF4H (MW 87.82) InChI = 1S/BF4/c2-1(3,4)5/q-1/p+1 InChIKey = ODGCEQLVLXJUCC-UHFFFAOYSA-O [67969-83-9] C2H7BF4O (MW 133.90) InChI = 1S/C2H6O.BF4/c1-3-2;2-1(3,4)5/h1-2H3;/q;-1/p+1 InChIKey = GOKRNJRKIGVPOV-UHFFFAOYSA-O [67969-82-8] C4H11BF4O (MW 161.96) InChI = 1S/C4H10O.BF4/c1-3-5-4-2;2-1(3,4)5/h3-4H2,1-2H3;/q;-1/p+1 InChIKey = JDQHPOVUCKSJFJ-UHFFFAOYSA-O (strong acid with pKa = −0.441 and a noncoordinating counterion2)Solubility: sol H2O, alcohols and ethers.Form Supplied in: 48% aq solution; diethyl ether complex; dimethyl ether complex.Purification: commercial 50% solutions can be concentrated by evaporation at 50–60 °C/5 mmHg to give a residue of 11 N total acidity. Water can also be removed by slow addition to ice-cold acetic anhydride (dangerously exothermic reaction: caution is advised!).3Handling, Storage, and Precautions: storage in glass containers is not recommended, although dilute solutions can be used in glass containers over short periods. Poisonous: causes burns to eyes, skin, and mucous membranes and may be fatal if ingested. Use in a fume hood with safety goggles and chemically resistant gloves and clothing. Incompatible with cyanides and strong bases: decomposes to form HF.
    No preview · Chapter · Apr 2001
  • Gregory K. Friestad · Bruce P. Branchaud

    No preview · Chapter · Apr 2001
  • Gregory K. Friestad · Bruce P. Branchaud
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    ABSTRACT: [13826-83-0] BF4H4N (MW 104.84) InChI = 1S/BF4.H3N/c2-1(3,4)5;/h;1H3/q-1;/p+1InChIKey = PDTKOBRZPAIMRD-UHFFFAOYSA-O(anion exchange reagent for preparation of isolable diazonium salts;1 weak acid with nonnucleophilic counterion; electrolyte useful for synthetic electrochemistry2)Physical Data: mp 220–230 °C (sublimes); d 1.871 g cm−3 at 15 °C.Solubility: sol H2O.Form Supplied in: white solid; widely available.Purification: crystallization from water (1 mL g−1) between 100 °C and 0 °C.Handling, Storage, and Precautions: toxic by ingestion and inhalation. Irritates and can burn skin, eyes, and mucous membranes. Avoid extreme heat. Ammonium tetrafluoroborate is incompatible with acids, oxidizers, and reducing agents. Decomposition products include fluorides, NOX, and NH3. Use in a fume hood with safety goggles and chemically resistant gloves and clothing. Use a dust respirator if much dust will be produced during use.
    No preview · Chapter · Apr 2001
  • B E Turner · B P Branchaud
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    ABSTRACT: Processing of trans-2-phenylcyclopropylmethanols 5 and 6 by the monocopper/tyrosine radical enzyme galactose oxidase led to mechanism-based inactivation with a partition ratio, (k(cat) + k(inact))/k(inact), of approximately 1 and a primary deuterium isotope effect, k(inact(H))/k(inact(D)), of 3.2. The data are consistent with a radical mechanism for galactose oxidase with a short lived ketyl radical anion intermediate.
    No preview · Article · Jan 2000 · Bioorganic & Medicinal Chemistry Letters

Publication Stats

2k Citations
233.03 Total Impact Points


  • 1988-2010
    • University of Oregon
      • • Department of Chemistry
      • • Materials Science Institute
      • • Institute of Molecular Biology
      Eugene, Oregon, United States
  • 2007
    • University of Pittsburgh
      • Department of Pharmacology and Chemical Biology
      Pittsburgh, PA, United States
  • 1998
    • Roche Institute of Molecular Biology
      Nutley, New Jersey, United States
  • 1985-1986
    • Massachusetts Institute of Technology
      Cambridge, Massachusetts, United States
  • 1983
    • Harvard University
      Cambridge, Massachusetts, United States