当前位置： SCI文献检索 > BIOCHEMISTRY期刊下所有文献 > Design and chemical synthesis of a magnetic resonance contrast agent with enhanced in vitro binding, high blood-brain barrier permeability, and in vivo targeting to Alzheimer's disease amyloid plaques.

Design and chemical synthesis of a magnetic resonance contrast agent with enhanced in vitro binding, high blood-brain barrier permeability, and in vivo targeting to Alzheimer's disease amyloid plaques.

Abstract：

:Molecular imaging is an important new direction in medical diagnosis; however, its success is dependent upon molecular probes that demonstrate selective tissue targeting. We report the design and chemical synthesis of a derivative of human amyloid-beta (Abeta) peptide that is capable of selectively targeting individual amyloid plaques in the brain of Alzheimer's disease transgenic mice after being intravenously injected. This derivative is based on the sequence of the first 30 amino acid residues of Abeta with asparagyl/glutamyl-4-aminobutane residues (N-4ab/Q-4ab) substituted at unique Asp and Glu positions and with Gd-DTPA-aminohexanoic acid covalently attached at the N-terminal Asp. The Gd[N-4ab/Q-4ab]Abeta30 peptide was homogeneous as shown by high-resolution analytical techniques with a mass of +/-4385 Da determined by electrospray ionization mass spectrometry. This diamine- and gadolinium-substituted derivative of Abeta is shown to have enhanced in vitro binding to Alzheimer's disease (AD) amyloid plaques and increased in vivo permeability at the blood-brain barrier because of the unique Asp/Glu substitutions. In addition, specific in vivo targeting to AD amyloid plaques is demonstrated throughout the brain of an APP, PS1 transgenic mouse after intravenous injection. Because of the magnetic resonance (MR) imaging contrast enhancement provided by gadolinium, this derivative should enable the in vivo MR imaging of individual amyloid plaques in the brains of AD animals or patients to allow for early diagnosis and also provide a direct measure of the efficacy of anti-amyloid therapies currently being developed.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Poduslo JF,Curran GL,Peterson JA,McCormick DJ,Fauq AH,Khan MA,Wengenack TM

doi

10.1021/bi0359574

subject

Has Abstract

pub_date

2004-05-25 00:00:00

pages

6064-75

issue

20

eissn

0006-2960

issn

1520-4995

journal_volume

43

pub_type

杂志文章

相关文献

BIOCHEMISTRY文献大全
  • Quantum Mechanics/Molecular Mechanics Simulations Identify the Ring-Opening Mechanism of Creatininase.

    abstract：:Creatininase catalyzes the conversion of creatinine (a biosensor for kidney function) to creatine via a two-step mechanism: water addition followed by ring opening. Water addition is common to other known cyclic amidohydrolases, but the precise mechanism for ring opening is still under debate. The proton donor in this...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/acs.biochem.7b01032

    authors： Jitonnom J,Mujika JI,van der Kamp MW,Mulholland AJ

    更新日期：2017-12-05 00:00:00

  • In vitro biosynthesis of a decasaccharide prototype of multiply branched polylactosaminoglycan backbones.

    abstract：:Multiply branched polylactosaminoglycans are expressed in glycoproteins and glycolipids of many cells. Interest in their biology stems from their abundant expression in early embryonal cells and from their ability to carry multiple lectin-binding determinants, which makes them prominent ligands and antagonists of cell...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi9627673

    authors： Leppanen A,Salminen H,Zhu Y,Maaheimo H,Helin J,Costello CE,Renkonen O

    更新日期：1997-06-10 00:00:00

  • Coordinating role of His216 in MgATP binding and cleavage in pyruvate carboxylase.

    abstract：:His216 is a well-conserved residue in pyruvate carboxylases and, on the basis of structures of the enzyme, appears to have a role in the binding of MgATP, forming an interaction with the 3'-hydroxyl group of the ribose ring. Mutation of this residue to asparagine results in a 9-fold increase in the Km for MgATP in its...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi4016814

    authors： Adina-Zada A,Jitrapakdee S,Wallace JC,Attwood PV

    更新日期：2014-02-18 00:00:00

  • Cooperativity of papain-substrate interaction energies in the S2 to S2' subsites.

    abstract：:Enzyme-substrate contacts in the hydrolysis of ester substrates by the cysteine protease papain were investigated by systematically altering backbone hydrogen-bonding and side-chain hydrophobic contacts in the substrate and determining each substrate's kinetic constants. The observed specificity energies [defined as d...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00219a033

    authors： Berti PJ,Faerman CH,Storer AC

    更新日期：1991-02-05 00:00:00

  • Glycolate formation catalyzed by spinach leaf transketolase utilizing the superoxide radical.

    abstract：:A homogeneous preparation of transketolase was obtained from spinach leaf; the specific enzyme activity was 9.5 mumolo of glyceraldehyde-3-P formed (mg of protein)-1 min-1, when xylulose-5-P and ribose-5-P were used as the donor and acceptor, respectively, of the ketol residue. Transketolase catalyzed the formation of...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00558a015

    authors： Takabe T,Asami S,Akazawa T

    更新日期：1980-08-19 00:00:00

  • Cyclopropane fatty acid synthase of Escherichia coli: deduced amino acid sequence, purification, and studies of the enzyme active site.

    abstract：:Cyclopropane fatty acid (CFA) synthase of Escherichia coli catalyzes a modification of the acyl chains of phospholipid bilayers. We report (i) identification of the CFA synthase protein, (ii) overproduction (> 600-fold) and purification to essential homogeneity of the enzyme, and (iii) the amino acid sequence of CFA s...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00160a011

    authors： Wang AY,Grogan DW,Cronan JE Jr

    更新日期：1992-11-17 00:00:00

  • Assignment of the 1H NMR spectrum and secondary structure elucidation of the single-stranded DNA binding protein encoded by the filamentous bacteriophage IKe.

    abstract：:By means of 2D NMR techniques, all backbone resonances in the 1H NMR spectrum of the single-stranded DNA binding protein encoded by gene V of the filamentous phage IKe have been assigned sequence specifically (at pH 4.6, T = 298 K). In addition, a major part of the side chain resonances could be assigned as well. Anal...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00119a039

    authors： van Duynhoven JP,Folkers PJ,Prinse CW,Harmsen BJ,Konings RN,Hilbers CW

    更新日期：1992-02-04 00:00:00

  • The colchicine-induced GTPase activity of tubulin: state of the product. Activation by microtubule-promoting cosolvents.

    abstract：:Colchicine induces a weak assembly-independent GTPase activity in calf brain tubulin [David-Pfeuty, T., Erickson, H. P., & Pantaloni, D. (1977) Proc. Natl. Acad. Sci. U.S.A. 74, 5372-5376; Andreu, J. M., & Timasheff, S. N. (1981) Arch. Biochem. Biophys. 211, 151-157]. Kinetic analysis shows a turnover number of 2 x 10...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00186a027

    authors： Perez-Ramirez B,Shearwin KE,Timasheff SN

    更新日期：1994-05-24 00:00:00

  • A monosaccharide is bound to the sodium pump alpha-subunit.

    abstract：:We have recently reported that the Na pump alpha-subunit has cytosolic-oriented oligosaccharides which were sensitive to cleavage by an enzyme specific for hydrolysis of N-linked glycans [Pedemonte et al. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 9789-9793]. We now describe experiments that characterize the saccharides...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00158a008

    authors： Pedemonte CH,Kaplan JH

    更新日期：1992-11-03 00:00:00

  • Phosphorus-31 nuclear magnetic resonance studies of the binding of nucleotides to NADP+-specific isocitrate dehydrogenase.

    abstract：:The interaction of the 2'-phosphate-containing nucleotides (NADP+, NADPH, 2'-phosphoadenosine 5'-diphosphoribose, and adenosine 2',5'-bisphosphate) with NADP+ -specific isocitrate dehydrogenase was studied by using 31P NMR spectroscopy. The separate resonances corresponding to free and bound nucleotides, characteristi...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00303a015

    authors： Mas MT,Colman RF

    更新日期：1984-04-10 00:00:00

  • GliP, a multimodular nonribosomal peptide synthetase in Aspergillus fumigatus, makes the diketopiperazine scaffold of gliotoxin.

    abstract：:The fungal metabolite gliotoxin has a redox-active disulfide bridge spanning carbons 3 and 6 of a diketopiperazine (DKP) scaffold. The proposed DKP synthetase, GliP, from Aspergillus fumigatus Af293, is a three module (A1-T1-C1-A2-T2-C2-T3) 236 kDa protein that can be overproduced in soluble form in Escherichia coli. ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi061845b

    authors： Balibar CJ,Walsh CT

    更新日期：2006-12-19 00:00:00

  • Local conformational transition of Hydrogenobacter thermophilus cytochrome c552 relevant to its redox potential.

    abstract：:In order to elucidate the molecular mechanisms responsible for the apparent nonlinear behavior of the temperature dependence of the redox potential of Hydrogenobacter thermophilus cytochrome c552 [Takahashi, Y., Sasaki, H., Takayama, S. J., Mikami, S., Kawano, S., Mita, H., Sambongi, Y., and Yamamoto, Y. (2006) Bioche...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi7000714

    authors： Takayama SJ,Takahashi YT,Mikami S,Irie K,Kawano S,Yamamoto Y,Hemmi H,Kitahara R,Yokoyama S,Akasaka K

    更新日期：2007-08-14 00:00:00

  • Correlation between the inhibition of the acto-heavy meromyosin ATPase and the binding of tropomyosin to F-actin: effects of Mg2+, KCl, troponin I, and troponin C.

    abstract：:When stoichiometric amounts of tropomyosin (TM) are bound to F-actin in the presence of 2 mM ATP, the MG2+-activated acto-heavy meromyosin (HMM) ATPase is inhibited by about 60% in 5 mM MgCl2-30 mM KCl. If the concentration of MgCl2 is reduced to 1 mM, the inhibition disappears because TM no longer binds to F-actin. I...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00683a025

    authors： Eaton BL,Kominz DR,Eisenberg E

    更新日期：1975-06-17 00:00:00

  • Structural polymorphism and dynamism in the DNA segment GATCTTCCCCCCGGAA: NMR investigations of hairpin, dumbbell, nicked duplex, parallel strands, and i-motif.

    abstract：:Structure and dynamism in a DNA segment d-GATCTTCCCCCCGGAA have been investigated by nuclear magnetic resonance (NMR) spectroscopy. At neutral pH, the molecule exists largely as a dumbbell, formed by the association of two hairpins with sticky ends. A small percentage of hairpin is also detectable. The stem of the dum...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi970819y

    authors： Singh S,Patel PK,Hosur RV

    更新日期：1997-10-28 00:00:00

  • Chemical cross-linking of heteromeric glucocorticoid receptors.

    abstract：:Glucocorticoid receptors of wild-type and nti ("increased nuclear transfer") mutant S49.1 mouse lymphoma cells exist in extracts under low-salt conditions predominantly as high molecular weight species (Mr greater than or equal to 300,000). These receptor-hormone complexes are unable to bind to DNA. High salt (300 mM ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00415a030

    authors： Rexin M,Busch W,Gehring U

    更新日期：1988-07-26 00:00:00

  • Catecholamine-stimulated guanosine 5'-O-(3-thiotriphosphate) binding to the stimulatory GTP-binding protein of adenylate cyclase: kinetic analysis in reconstituted phospholipid vesicles.

    abstract：:The stimulatory GTP-binding protein of adenylate cyclase, Gs, and beta-adrenergic receptors were reconstituted into unilamellar phospholipid vesicles. The kinetics of the quasiirreversible binding of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) to Gs, equivalent to Gs activation by nucleotide, was studied with re...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00318a014

    authors： Asano T,Ross EM

    更新日期：1984-11-06 00:00:00

  • Crystal structure and properties of CYP231A2 from the thermoacidophilic archaeon Picrophilus torridus.

    abstract：:The crystal structure of a cytochrome P450 from the thermoacidophile Picrophilus torridus, CYP231A2 (PTO1399), has been solved. This structure reveals a wide open substrate access channel. To better understand ligand-induced structural transitions in CYP231A2, protein-ligand interactions were investigated using 4-phen...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi702240k

    authors： Ho WW,Li H,Nishida CR,de Montellano PR,Poulos TL

    更新日期：2008-02-19 00:00:00

  • Composition and structure of zinc-deficient Euglena gracilis chromatin.

    abstract：:The histone content of zinc-deficient (-Zn) Euglena gracilis decreases while, concomitantly, DNA content increases and the transcription rate is reduced markedly [Mazus, B., Falchuk, K. H., & Vallee, B. L. (1983) Biochemistry (in press); Falchuk, K. H., Fawcett, D. W., & Vallee, B. L. (1975) J. Cell Sci. 17, 57-78]. T...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00291a014

    authors： Stankiewicz AJ,Falchuk KH,Vallee BL

    更新日期：1983-10-25 00:00:00

  • Targeted generation of DNA strand breaks using pyrene-conjugated triplex-forming oligonucleotides.

    abstract：:Gene targeting by triplex-forming oligonucleotides (TFOs) has proven useful for gene modulation in vivo. Photoreactive molecules have been conjugated to TFOs to direct sequence-specific damage in double-stranded DNA. However, the photoproducts are often repaired efficiently in cells. This limitation has led to the sea...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi7024029

    authors： Benfield AP,Macleod MC,Liu Y,Wu Q,Wensel TG,Vasquez KM

    更新日期：2008-06-10 00:00:00

  • Inhibition and binding kinetics of the hepatitis C virus NS3 protease inhibitor ITMN-191 reveals tight binding and slow dissociative behavior.

    abstract：:The protease activity of hepatitis C virus nonstructural protein 3 (NS3) is essential for viral replication. ITMN-191, a macrocyclic inhibitor of the NS3 protease active site, promotes rapid, multilog viral load reductions in chronic HCV patients. Here, ITMN-191 is shown to be a potent inhibitor of NS3 with a two-step...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi900038p

    authors： Rajagopalan R,Misialek S,Stevens SK,Myszka DG,Brandhuber BJ,Ballard JA,Andrews SW,Seiwert SD,Kossen K

    更新日期：2009-03-24 00:00:00

  • Estimating the degree of expansion in the transition state for protein unfolding: analysis of the pH dependence of the rate constant for caricain denaturation.

    abstract：:The thermal denaturation of caricain (the most alkaline of papain-related proteinases) was studied in acid media. Under all conditions tested, caricain denatured irreversibly following a single first-order reaction that involves simultaneous loss of secondary and tertiary structures. Besides, variation of the rate con...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi991658w

    authors： López-Arenas L,Solís-Mendiola S,Hernández-Arana A

    更新日期：1999-11-30 00:00:00

  • A typical preparation of Francisella tularensis O-antigen yields a mixture of three types of saccharides.

    abstract：:Tularemia is a severe infectious disease in humans caused by the Gram-negative bacterium Francisella tularensis (Ft). Because of its low infectious dose, high mortality rate, and the threat of its large-scale dissemination in weaponized form, development of vaccines and immunotherapeutics against Ft is essential. Ft l...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi201450v

    authors： Wang Q,Shi X,Leymarie N,Madico G,Sharon J,Costello CE,Zaia J

    更新日期：2011-12-20 00:00:00

  • Selective incorporation of nitrile-based infrared probes into proteins via cysteine alkylation.

    abstract：:The nitrile stretching vibration is increasingly used as a sensitive infrared probe of local protein environments. However, site-specific incorporation of a nitrile moiety into proteins is difficult. Here we show that various aromatic nitriles can be easily incorporated into peptides and proteins via either thiol alky...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi101711a

    authors： Jo H,Culik RM,Korendovych IV,Degrado WF,Gai F

    更新日期：2010-12-14 00:00:00

  • Structure of glucagon-like peptide (7-36) amide in a dodecylphosphocholine micelle as determined by 2D NMR.

    abstract：:We have used 2D 1H NMR to determine the structure of glucagon-like peptide-1-(7-36) amide bound to a dodecylphosphocholine micelle. In this membranelike environment, the peptide hormone is shown to have a structure similar to that observed for glucagon. It consists of an N-terminal random coil segment (residues 1-7), ...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00178a009

    authors： Thornton K,Gorenstein DG

    更新日期：1994-03-29 00:00:00

  • Ligand binding properties of bacterial hemoglobins and flavohemoglobins.

    abstract：:Bacterial hemoglobins and flavohemoglobins share a common globin fold but differ otherwise in structural and functional aspects. The bases of these differences were investigated through kinetic studies on oxygen, carbon monoxide, and nitric oxide binding. The novel bacterial hemoglobins from Clostridium perfringens an...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi047389d

    authors： Farrés J,Rechsteiner MP,Herold S,Frey AD,Kallio PT

    更新日期：2005-03-15 00:00:00

  • Escherichia coli single-stranded DNA binding protein is mobile on DNA: 1H NMR study of its interaction with oligo- and polynucleotides.

    abstract：:The interaction of the Escherichia coli single-stranded DNA binding protein (SSB) with oligo- and poly-nucleotides has been studied by 270-MHz 1H NMR spectroscopy and fast kinetic techniques. d(pT)8 and poly(dT) were used to study noncooperative and cooperative binding, respectively. The H6, H1', and CH3 resonances of...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00320a036

    authors： Römer R,Schomburg U,Krauss G,Maass G

    更新日期：1984-12-04 00:00:00

  • Structural effects in reactivity and adduct formation of polycyclic aromatic epoxide and diol epoxide derivatives with DNA: comparison between 1-oxiranylpyrene and benzo[a]pyrenediol epoxide.

    abstract：:Reaction of 1-oxiranylpyrene (1-OP) with DNA and the structures of the covalent and noncovalent complexes formed were studied in aqueous media (5 mM phosphate buffer with 0.1 M NaCl, pH 7) by utilizing the techniques of absorption, fluorescence and linear dichroism spectroscopy in order to gain an understanding of pos...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00318a009

    authors： Kim MH,Geacintov NE,Pope M,Harvey RG

    更新日期：1984-11-06 00:00:00

  • Time-resolved fluorescence resonance energy transfer shows that the bacterial multidrug ABC half-transporter BmrA functions as a homodimer.

    abstract：:Members of the ATP-binding cassette (ABC) transporters share the same basic architecture, with a four-core domain made of two transmembrane plus two nucleotide-binding domains. However, a supramolecular organization has been detected in some ABC transporters, which might be relevant to physiological regulation of subs...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi0482809

    authors： Dalmas O,Do Cao MA,Lugo MR,Sharom FJ,Di Pietro A,Jault JM

    更新日期：2005-03-22 00:00:00

  • Assembly of an exceptionally stable RNA tertiary interface in a group I ribozyme.

    abstract：:Group I intron RNAs contain a core of highly conserved helices flanked by peripheral domains that stabilize the core structure. In the Tetrahymena group I ribozyme, the P4, P5, and P6 helices of the core pack tightly against a three-helix subdomain called P5abc. Chemical footprinting and the crystal structure of the T...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi982113p

    authors： Doherty EA,Herschlag D,Doudna JA

    更新日期：1999-03-09 00:00:00

  • Indoleglycerol phosphate synthase-phosphoribosyl anthranilate isomerase: comparison of the bifunctional enzyme from Escherichia coli with engineered monofunctional domains.

    abstract：:Putative domain--domain interactions of the monomeric bifunctional enzyme indoleglycerol phosphate synthase:phosphoribosyl anthranilate isomerase from Escherichia coli were probed by separating the domains on the gene level and expressing them as monofunctional proteins. The engineered monofunctional enzymes were foun...

    journal_title：Biochemistry

    pub_type： 杂志文章

    doi：10.1021/bi00016a013

    authors： Eberhard M,Tsai-Pflugfelder M,Bolewska K,Hommel U,Kirschner K

    更新日期：1995-04-25 00:00:00