Hiroshi Abe

Tsinghua University, Beijing, Beijing Shi, China

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Publications (8)16.92 Total impact

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    ABSTRACT: In the brains of Alzheimer's disease patients, the tau protein dissociates from the axonal microtubule and abnormally aggregates to form a paired helical filament (PHF). One of the priorities in Alzheimer research is to determine the effects of abnormal phosphorylation on the local structure. A series of peptides corresponding to isolated regions of tau protein have been successfully synthesized using Fmoc-based chemistry and their conformations were determined by 1H NMR spectroscopy and circular dichroism (CD) spectroscopy. Immunodominant peptides corresponding to tau-(256-273), tau-(350-367) and two phosphorylated derivatives in which a single Ser was phosphorylated at positions 262 and 356, respectively, were the main focus of the study. A direct alteration of the local structure after phosphorylation constitutes a new strategy through which control of biological activity can be enforced. In our study on Ser262 in R1 peptide and Ser356 in R4 peptide, phosphorylation modifies both the negative charge and the local conformation nearby the phosphorylation sites. Together, these structural changes indicate that phosphorylation may act as a conformational switch in the binding domain of tau protein to alter specificity and affinity of binding to microtubule, particularly in response to the abnormal phosphorylation events associated with Alzheimer's disease.
    Regulatory Peptides 09/2005; 130(1-2):48-56. · 2.06 Impact Factor
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    ABSTRACT: Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry was used to obtain spectra of peptide-DNA complexes formed by basic domain (BD15) of c-Fos protein and DNA AP-1 site (5'-TGAGTCA-3'). The noncovalent interaction between single stranded DNA and BD15 was observed and confirmed to be an ionic one between the negatively charged sugar-phosphate backbone of DNA and positively charged side chains of Arg- and lys-rich peptides as demonstrated by Vertes and coworkers and Woods and coworkers. But the specific noncovalent interaction between DNA AP-1 site and the dimer of BD15 was firstly detected in this paper. Various different sequence DNAs were studied and it was found that this interaction is a sequence-specific one, and AP-1 site was essential for this interaction. This specific interaction depends on the matrix. It was only observed in the ATT matrix and not in the other two matrixes (CHCA and DHBA).
    Journal of the American Society for Mass Spectrometry 02/2004; 15(1):28-31. · 3.59 Impact Factor
  • Hiroshi Abe, Hiroshi Nakanishi
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    ABSTRACT: The formation of aggregates including amyloid fibrils in the peptide fragment of non-amyloid-beta component (NAC(1-13)) was investigated under a variety of solution conditions. Two types of sample preparation method from neutral and acidic conditions were examined. Electron microscopy observation showed amorphous aggregates in the sample at pH 4.5 adjusted from the neutral condition. The CD and HPLC quantitative analyses indicated that the formation of the amorphous aggregate did not accompany a conformational conversion from a random coil in the sample solution. The analyses of pKa values determined by pH titration experiments in NMR spectroscopy indicated that the protonation of the carboxyl group of the N-terminal glutamic acid triggers the aggregation of NAC(1-13). On the other hand, electron microscopy observation showed that the samples at pH 2.2 and 4.5 adjusted from an initial pH of 2.2 form fibrils. A beta-structure was detected by CD spectroscopy in the 1 mM NAC(1-13) at pH 2.2 immediately after preparation. The CD analyses of samples at different concentrations and temperatures indicated that 1 mM NAC(1-13) immediately after preparation at pH 2.2 was oligomerized. The quantity of the beta-structure was increased depending on the Incubation time. The results strongly suggested that the beta-conformational oligomers play a critical role for the fibril nucleus.
    Journal of Peptide Science 04/2003; 9(3):177-86. · 2.07 Impact Factor
  • Hiroshi Abe, Hiroshi Nakanishi
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    ABSTRACT: A peptide fragment of a non-amyloid-beta component (NAC(1-13)) was studied by CD and electron microscopy. Typical amyloid fibrils were observed by EM in a solution of NAC(1-13). In addition to the beta-structural CD band in the far-UV region, a novel CD band near 285 nm was observed in a peptide solution of NAC(1-13). Taking the NAC(1-13) to contain neither an aromatic amino acid residue nor cystine into account, the CD band can be attributed to amyloid fibrils of NAC(1-13).
    Analytical Sciences 02/2003; 19(1):171-3. · 1.57 Impact Factor
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    ABSTRACT: The conformational transition to a beta-structure and the aggregation process of Alzheimer amyloid beta-peptide (12-24) [abbreviated as A beta(12-24)] were studied. The influence of sample dissolution methods for the aggregate structure was examined by electron microscopy (EM). The difference in the width of the aggregate of A beta(12-24) depended on the pH immediately after sample dissolution. Two types of sample dissolution methods, F and R, were employed. For dissolution method F, the peptide sample was immediately dissolved in water and then adjusted to pH 2.2 by adding buffer, while for dissolution method R, the peptide was directly dissolved in the buffer solution. In the latter case, the starting pH was 3.0. Slight fibrils (10-12 nm in diameter) were observed with method F, and wider ribbon-like aggregates (17-20 nm in diameter) with method R, despite the same pH range. A difference between methods F and R was also detected in the CD spectra, especially at pHs near 5.0. The CD intensity of the 214 nm band with method R changed with pH, with the highest value at pH 3.7, whereas that with method F was unchanged at pHs below 5.0. The temperature-dependent CD results showed that a thermostable aggregate of A beta(12-24) occurs at higher pHs than 3.0. NMR analysis showed that deprotonation of the C-terminal carboxylate group in A beta(12-24) triggered the aggregate formation, and the transition from a random coil to a beta-conformation in the C-terminal region of V18-V24 was detected on analysis of the (3)Ja(N) coupling constant in the pH range of 2.2 to 3.0.
    Journal of Biochemistry 01/2003; 132(6):863-74. · 3.07 Impact Factor
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    ABSTRACT: The symmetry phosphoramidite reagents were synthesized via a two-step route and used for the ‘one pot’ synthesis of the phosphoserine building block Fmoc-Ser(PO(OBzl)OH)-OH. The procedure is simple and rapid, and product is obtained in high yield. When using this building block, the phosphopeptide (RKGS(PO3H2)SSNEPSSDSLSSPTLLAL) related to the C-terminal of c-Fos protein was synthesized manually by Fmoc/t-Bu procedure and characterized by matrix assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. In the fragment ion of phosphopeptide in the MALDI-TOF mass spectrometry with a curved field reflection, the acquired information can be used to identify the sequences and the phosphorylation sites of the peptide.
    Letters in Peptide Science 01/2003; 10(1):57-62.
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    ABSTRACT: Polymerization of the amyloid beta-peptide (Abeta) has been identified as a major feature of the pathogenesis of Alzheimer's disease (AD). Inhibition of the formation of these toxic polymers of Abeta has emerged as an approach for developing therapeutics for AD. NMR and CD spectra were used to investigate the interaction between cyclodextrin and Abeta(12-28) peptide, which was reported to be an important region for forming amyloid fibrils. CD spectral analyses show that of the alpha-, beta- and gamma-cyclodextrins only beta-cyclodextrin inhibits the aggregation of Abeta(12-28) at pH 5.0. Analysis of the one-dimensional proton NMR spectra of Abeta(12-28) and the mixture of Abeta(12-28) with beta-cyclodextrin clearly indicates that there are chemical shift changes in the aromatic ring of Phe19 and the methyl groups of Val18 in the peptide. The NOESY spectra show cross-peaks between H-3 and H-5 of beta-cyclodextrin and the aromatic protons of Phe19 and Phe20. These chemical shift differences and NOEs demonstrate that there is an interaction between Abeta(12-28) and beta-cyclodextrin. Analysis of the cross-peak intensity in the NOESY spectra reveals that the aromatic rings of Phe19 and 20 are generally inserted into beta-cyclodextrin at the broad side and are oriented toward the narrow side of the cavity.
    Biochemical and Biophysical Research Communications 11/2002; 297(4):1011-15. · 2.28 Impact Factor
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    ABSTRACT: Polymerization of the amyloid β-peptide (Aβ) has been identified as a major feature of the pathogenesis of Alzheimer’s disease (AD). Inhibition of the formation of these toxic polymers of Aβ has emerged as an approach for developing therapeutics for AD. NMR and CD spectra were used to investigate the interaction between cyclodextrin and Aβ(12–28) peptide, which was reported to be an important region for forming amyloid fibrils. CD spectral analyses show that of the α-, β- and γ-cyclodextrins only β-cyclodextrin inhibits the aggregation of Aβ(12–28) at pH 5.0. Analysis of the one-dimensional proton NMR spectra of Aβ(12–28) and the mixture of Aβ(12–28) with β-cyclodextrin clearly indicates that there are chemical shift changes in the aromatic ring of Phe19 and the methyl groups of Val18 in the peptide. The NOESY spectra show cross-peaks between H-3 and H-5 of β-cyclodextrin and the aromatic protons of Phe19 and Phe20. These chemical shift differences and NOEs demonstrate that there is an interaction between Aβ(12–28) and β-cyclodextrin. Analysis of the cross-peak intensity in the NOESY spectra reveals that the aromatic rings of Phe19 and 20 are generally inserted into β-cyclodextrin at the broad side and are oriented toward the narrow side of the cavity.
    Biochemical and Biophysical Research Communications 10/2002; 297(4):1011-1015. · 2.28 Impact Factor

Publication Stats

60 Citations
16.92 Total Impact Points

Institutions

  • 2004–2005
    • Tsinghua University
      • Department of Chemistry
      Beijing, Beijing Shi, China
  • 2002–2005
    • National Institute of Advanced Industrial Science and Technology
      • Biomedicinal Information Research Center
      Tsukuba, Ibaraki, Japan