Abstract：
:Cellular toxicity resulting from nucleation-dependent polymerization of amyloid beta-peptide (Abeta) is considered to be a major and possibly the primary component of Alzheimer's disease (AD). Inhibition of Abeta polymerization has thus been identified as a target for the development of therapeutic agents for the treatment of AD. The intrinsic affinity of Abeta for itself suggested that Abeta-specific interactions could be adapted to the development of compounds that would bind to Abeta and prevent it from polymerizing. Abeta-derived peptides of fifteen residues were found to be inhibitory of Abeta polymerization. The activity of these peptides was subsequently enhanced through modification of their amino termini with specific organic reagents. Additional series of compounds prepared to probe structural requirements for activity allowed reduction of the size of the inhibitors and optimization of the Abeta-derived peptide portion to afford a lead compound, cholyl-Leu-Val-Phe-Phe-Ala-OH (PPI-368), with potent polymerization inhibitory activity but limited biochemical stability. The corresponding all-D-amino acyl analogue peptide acid (PPI-433) and amide (PPI-457) retained inhibitory activity and were both stable in monkey cerebrospinal fluid for 24 h.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Findeis MA,Musso GM,Arico-Muendel CC,Benjamin HW,Hundal AM,Lee JJ,Chin J,Kelley M,Wakefield J,Hayward NJ,Molineaux SMdoi
10.1021/bi982824nsubject
Has Abstractpub_date
1999-05-25 00:00:00pages
6791-800issue
21eissn
0006-2960issn
1520-4995pii
bi982824njournal_volume
38pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract：:The guanyl nucleotide binding regulatory protein of retinal rod outer segments, called Gt, that couples the photon receptor rhodopsin with the light-activated cGMP phosphodiesterase, can be resolved into two functional components, alpha t and beta gamma t. The effect of monoclonal antibody binding to the alpha t subun...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00451a047
更新日期：1989-12-12 00:00:00
abstract：:Propeptide processing occurs in specific compartments of the secretory pathway, but how these processing-competent organelles are generated from their processing-incompetent precursor compartments is unknown. To dissect the process biochemically, we have developed a novel cell-free system reconstituting the production...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0112762
更新日期：2001-10-30 00:00:00
abstract：:ALY is a ubiquitously expressed nuclear protein which interacts with proteins such as TAP that are involved in export of mRNA from the nucleus to the cytoplasm, as well as with proteins that bind the T cell receptor alpha gene enhancer. ALY has also been shown to bind mRNA and to co-localize in the nucleus with compon...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi034062o
更新日期：2003-06-24 00:00:00
abstract：:Blood coagulation is initiated by Ca(2+)-dependent binding of coagulation factor VIIa (FVIIa) to its cofactor, tissue factor (TF). The TF:FVIIa complex activates factors IX and X, ultimately leading to the formation of thrombin and the coagulation of blood. FVII consists of an N-terminal gamma-carboxyglutamic-acid-con...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi980522f
更新日期：1998-07-28 00:00:00
abstract：:Mild acid hydrolysis of Hafnia alvei strain 2 lipopolysaccharide released no O-specific polysaccharide but instead gave a monomeric octasaccharide repeating unit with N-acetylneuraminic acid as the reducing terminus. In addition, a dimer of the octasaccharide repeating unit, and also a decasaccharide composed of a fra...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00234a027
更新日期：1991-05-21 00:00:00
abstract：:Escherichia coli PurK, a dimeric N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) synthetase, catalyzes the conversion of 5-aminoimidazole ribonucleotide (AIR), ATP, and bicarbonate to N5-CAIR, ADP, and Pi. Crystallization of both a sulfate-liganded and the MgADP-liganded E. coli PurK has resulted in structures at 2....
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi991618s
更新日期：1999-11-23 00:00:00
abstract：:A solubilized preparation of steroid 5 alpha-reductase (EC 1.3.1.30) from rat liver has been used in studies focused toward an understanding of the kinetic mechanism associated with enzyme catalysis. From the results of analyses with product and dead-end inhibitors, a preferentially ordered binding of substrates and r...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00463a025
更新日期：1990-03-20 00:00:00
abstract：:PHD2 is a 2-oxoglutarate, non-heme Fe(2+)-dependent oxygenase that senses O2 levels in human cells by hydroxylating two prolyl residues in the oxygen-dependent degradation domain (ODD) of HIF1α. Identifying the active site contacts that determine the rate of reaction at limiting O2 concentrations is crucial for unders...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi501540c
更新日期：2015-05-12 00:00:00
abstract：:In order to evaluate the contributions that histidine residues might play both in the catalytic activities of endonuclease V and in binding to nontarget DNA, the technique of oligonucleotide site directed mutagenesis was used to create mutations at each of the four histidine residues in the endonuclease V gene. Althou...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00246a025
更新日期：1991-08-13 00:00:00
abstract：:Transcarboxylase (TC) is a multisubunit enzyme that catalyzes the transfer of a carboxylate group from methylmalonyl-CoA (MMCoA) to pyruvate. The CO2- group is shuttled between the MMCoA and pyruvate binding sites by a biotin cofactor, covalently linked to the 1.3S subunit. Fully carboxylated 1.3S can be prepared in v...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0116442
更新日期：2002-02-19 00:00:00
abstract：:Recombinant human 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthetase, isoform 1 (brain), was purified to near-homogeneity from an Escherichia coli expression system and kinetically characterized. The native enzyme, a dimer with each 71 kDa subunit containing an adenosine triphosphate (ATP) sulfurylase and an aden...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi049827m
更新日期：2004-04-13 00:00:00
abstract：:To study the substrate specificity and mechanism of thioltransferase (TTase) catalysis, we have used 14C- and 35S-radiolabeled mixed disulfides of cysteine and glutathione (GSH) with various cysteine-containing proteins. These protein mixed disulfide substrates were incubated with glutathione, glutathione disulfide (G...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00064a021
更新日期：1993-04-06 00:00:00
abstract：:A human genomic DNA library was screened for the gene coding for the gamma chain of fibrinogen by using a human cDNA for the gamma chain as a hybridization probe. The gene was identified in three overlapping recombinant lambda bacteriophage, and its sequence, including the immediate 5' and 3' flanking regions, was det...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00329a041
更新日期：1985-04-09 00:00:00
abstract：:The solution conformation is presented for representatives of each of the major classes of asparaginyl oligosaccharides. In this report the conformation of alpha(1-3)-, alpha(1-2)-, beta(1-2)-, and beta(1-4)-linked units is described. The conformational properties of these glycopeptides were determined by high-resolut...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00284a021
更新日期：1983-07-19 00:00:00
abstract：:Thiocyanate reacts noncatalytically with myeloperoxidase-derived HOCl to produce hypothiocyanite (OSCN(-)), thereby potentially limiting the propensity of HOCl to inflict host tissue damage that can lead to inflammatory diseases. However, the efficiency with which SCN(-) captures HOCl in vivo depends on the concentrat...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi902089w
更新日期：2010-03-09 00:00:00
abstract：:Conformational and environmental changes in the functionally significant amino-terminal region of human parathyroid hormone (hPTH), induced by solvent or by complexation with acidic lipid, have been investigated. Structural perturbations were monitored by their effect on the fluorescence decay kinetics of the single t...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00152a032
更新日期：1992-09-22 00:00:00
abstract：:The reaction of mushroom (Agaricus bisporus) tyrosinase with dioxygen in the presence of several o-diphenolic substrates has been studied by steady-state and transient-phase kinetics in order to elucidate the rate-limiting step and to provide new insights into the mechanism of oxidation of these substrates. A kinetic ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi000539+
更新日期：2000-08-29 00:00:00
abstract：:The expression level of protein DR1199 is observed to increase considerably in the radio-resistant bacterium Deinococcus radiodurans following irradiation. This protein belongs to the DJ-1 superfamily, which includes proteins with diverse functions, such as the archaeal proteases PhpI and PfpI, the bacterial chaperone...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi800882v
更新日期：2008-11-04 00:00:00
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
更新日期：1980-08-19 00:00:00
abstract：:Under mildly acidic conditions, annexin 12 (ANX) inserts into lipid membranes to form a transbilayer pore [Langen, R., et al. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 14060]. In this study, we have addressed the question of the oligomeric state of ANX in this transbilayer conformation by means of Forster-type resonanc...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi047805u
更新日期：2005-03-08 00:00:00
abstract：:The aldehyde oxidoreductase from Desulfovibrio gigas belongs to the family of molybdenum hydroxylases. Besides a molybdenum cofactor which constitutes their active site, these enzymes contain two [2Fe-2S](2+,1+) clusters which are believed to transfer the electrons provided by the substrate to an acceptor which is eit...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0510025
更新日期：2005-08-30 00:00:00
abstract：:In order to more clearly define the structure of human plasma fibronectin (PFn) under physiologic buffer conditions, we determined the mean harmonic rotational relaxation times (rho H) of PFn and the thrombin-derived 190/170-kDa PFn fragment using steady-state fluorescence polarization. These measurements utilized the...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00464a027
更新日期：1990-03-27 00:00:00
abstract：:The neonatal Fc receptor (FcRn) binds maternal immunoglobulin G (IgG) during the acquisition of passive immunity by the fetus or newborn. In adult mammals, FcRn also binds IgG and returns it to the bloodstream, thus protecting IgG from a default degradative pathway. Biosensor assays have been used to characterize the ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi970841r
更新日期：1997-08-05 00:00:00
abstract：:A new specific voltage-sensitive calcium channel (VSCC) blocker has been isolated from the venom of the fish-hunting cone snail Conus consors. This peptide, named omega-Ctx CNVIIA, consists of 27 amino acid residues folded by 3 disulfide bridges. Interestingly, loop 4, which is supposed to be crucial for selectivity, ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi002871r
更新日期：2001-12-04 00:00:00
abstract：:Matrix metalloproteinase-13 (MMP-13) is important in the pathology of osteoarthritis (OA). Although MMP-13 is considered a therapeutic target for OA, it is unclear how MMP-13 activity is regulated by the system that comprises various proteinases and their inhibitors. MMP-13 neutralizing antibodies could be a useful to...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi301228d
更新日期：2012-11-06 00:00:00
abstract：:The structural underpinnings of enzyme substrate specificity are investigated in a pair of copper amine oxidases (CAOs) from Hansenula polymorpha (HPAO-1 and HPAO-2). The X-ray crystal structure (to 2.0 A resolution) and steady state kinetic data of the second copper amine oxidase (HPAO-2) are presented for comparison...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi901933d
更新日期：2010-03-23 00:00:00
abstract：:A recently discovered bifunctional antibiotic-resistance enzyme named AAC(3)-Ib/AAC(6')-Ib', from Pseudomonas aeruginosa, catalyzes acetylation of aminoglycoside antibiotics. Since both domains are acetyltransferases, each was cloned and purified for mechanistic studies. The AAC(3)-Ib domain appears to be highly speci...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi700111z
更新日期：2007-05-01 00:00:00
abstract：:Bacteriophage T7 RNA polymerase is a single-subunit enzyme which has a C-terminal amino acid sequence of Phe-Ala-Phe-Ala883 (FAFA883). Closely related hydrophobic sequences are present at the C termini of seven other single-subunit RNA polymerases, including the mitochondrial RNA polymerase. Mutations at any of the fo...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi962397i
更新日期：1997-03-11 00:00:00
abstract：:Site-directed mutagenesis has been used to construct three recombinant mutant hemoglobins (rHbs), rHb(beta L105W), rHb(alpha D94A/betaL105W), and rHb(alpha D94A). rHb(beta L105W) is designed to form a new hydrogen bond from beta 105Trp to alpha 94Asp in the alpha(1)beta(2) subunit interface to lower the oxygen binding...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi001115i
更新日期：2000-11-14 00:00:00
abstract：:Extracts of two human glioma cell lines (lacking O6-methylguanine DNA-methyltransferase) (i.e., A1235 and its alkylation-resistant derivative A1235-MR4) were examined for their ability to execute strand incision at different base mismatches in model (45-bp) DNA. These heteroduplex substrates were of the same sequence ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi020239n
更新日期：2002-07-23 00:00:00
