Solution Structure of Residues 1-28 of the Amyloid .beta.-Peptide

Talafous, Joseph; Marcinowski, Keith J.; Klopman, Gilles; Zagorski, Michael G.

doi:10.1021/bi00191a006

Cited by 148 publications

(206 citation statements)

References 87 publications

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“…There is also a weak NOE between the upfield 5′H and the 4′CH 2 . In the NOESY spectrum of the peptide alone ( Figure 6B), the NOEs are analogous to spectra that we published earlier (Talafous et al, 1994), and the assignments of the Lys16 side chain resonances are shown along the diagonal. For the NOESY spectrum of the mixture ( Figure 6C), other than the His residues, there are no apparent changes in chemical shifts for the peptide resonances, and new NOEs were not detected between the peptide and nicotine.…”

Section: Shown Insupporting

confidence: 61%

“…In the past our laboratory has used these methods for studies of the -peptide [see Talafous et al (1994) and references cited therein]. The results shown here establish that these methods can be successfully applied to investigate inhibitors of -amyloidosis and their binding properties.…”

Section: Biological Functions Of Nicotine and Its Relevance To Alzheimentioning

confidence: 53%

“…To further improve the resolution, before Fourier transformation spectra were multiplied by a Lorentzian-to-Gaussian weighting factor. The majority of the 1 H NMR peaks of the -(1-28) peptide in aqueous SDS-d 25 solution were assigned and briefly described by us in an earlier publication (Talafous et al, 1994). The 1 H NMR peaks of nicotine in D 2 O containing 20 mM SDS-d 25 were assigned at 30.0°C using a standard absolute value two-dimensional (2D) COSY spectrum (Wüthrich, 1986).…”

Section: Sample Preparationmentioning

confidence: 99%

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Nicotine Inhibits Amyloid Formation by the β-Peptide

et al. 1996

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The 42-residue -(1-42) peptide is the major protein component of amyloid plaque cores in Alzheimer's disease. In aqueous solution at physiological pH, the synthetic -(1-42) peptide readily aggregates and precipitates as oligomeric -sheet structures, a process that occurs during amyloid formation in Alzheimer's disease. Using circular dichroism (CD) and ultraviolet spectroscopic techniques, we show that nicotine, a major component in cigarette smoke, inhibits amyloid formation by the -(1-42) peptide. The related compound cotinine, the major metabolite of nicotine in humans, also slows down amyloid formation, but to a lesser extent than nicotine. In contrast, control substances pyridine and Nmethylpyrrolidine accelerate the aggregation process. Nuclear magnetic resonance (NMR) studies demonstrate that nicotine binds to the 1-28 peptide region when folded in an R-helical conformation. On the basis of chemical shift data, the binding primarily involves the N-CH 3 and 5′CH 2 pyrrolidine moieties of nicotine and the histidine residues of the peptide. The binding is in fast exchange, as shown by single averaged NMR peaks and the lack of nuclear Overhauser enhancement data between nicotine and the peptide in two-dimensional NOESY spectra. A mechanism is proposed, whereby nicotine retards amyloidosis by preventing an R-helix f -sheet conformational transformation that is important in the pathogenesis of Alzheimer's disease.

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Section: Shown Insupporting

confidence: 61%

Section: Biological Functions Of Nicotine and Its Relevance To Alzheimentioning

confidence: 53%

Section: Sample Preparationmentioning

confidence: 99%

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Nicotine Inhibits Amyloid Formation by the β-Peptide

et al. 1996

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“…NMR is an excellent technique for determining the high resolution structure of peptides, but early NMR studies of the A␤ were hindered by the strong tendency of this peptide to aggregate, particularly near pH 5, where it forms a ␤-sheet-rich oligomer that precipitates. This obstacle was first surmounted by the pioneering studies of Zagorski and co-workers, who used cosolvents (18) and detergents (19) to solubilize monomeric A␤. NMR studies of monomeric A␤ in organic solvents (20), in cosolvents (18,21), or associated with detergent micelles (19,(22)(23)(24) revealed extensive helix formation.…”

mentioning

confidence: 99%

Alzheimer's Aβ40 Studied by NMR at Low pH Reveals That Sodium 4,4-Dimethyl-4-silapentane-1-sulfonate (DSS) Binds and Promotes β-Ball Oligomerization

Laurents

Gorman

Guo

et al. 2005

Journal of Biological Chemistry

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The Alzheimer's A␤40 peptide forms soluble oligomers that are extremely potent neurotoxins and strongly impede synapses function. In this study the formation and structure of the large, soluble, neurotoxic A␤40 oligomer called "␤-ball" were characterized by two-dimensional NMR, circular dichroism, fluorescence spectroscopy, hydrogen exchange, and equilibrium sedimentation. In acidic aqueous solution, half the A␤40 molecules are in the ␤-ball state; the remainder are monomeric. The equilibrium between the two states is slow as judged by NMR linewidths and is stable for months. The kinetics of ␤-ball formation from monomer are biphasic with 1 ‫؍‬ 7 min and 2 ‫؍‬ 80 min with no transient helix formation. Monomeric A␤40 is essentially devoid of stable secondary structure, although the central, Leu 17 -Ala 21 , and Cterminal, Gly 29 -Val 40 , hydrophobic regions show propensity toward adopting extended structure, and residues 22-25 tended to form a turn. We found that sodium 4,4-dimethyl-4-silapentane-1-sulfonate (DSS) binds to the central hydrophobic region of monomeric A␤40. DSS binds ␤-balls more strongly and caused them to double in size. Plausible micelle-like models for the ␤-ball structure with and without bound DSS are presented.

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“…The amyloid ß (1-28) peptide obtained from the protein data bank (PDB) has several confor mational structures determined via NMR in solu tion (Barrow and Zagorski, 1991;Zagorski and Barrow, 1992;Talafous et al, 1994). These struc-tures have been averaged and the starting coordi nates for this peptide were obtained and used to perform the calculations of water accessibility to the aspartyl residues at positions 7 and 23.…”

Section: Methodsmentioning

confidence: 99%

Solvent Accessibility to Aspartyl and Succinimidyl Residues at Positions 7 and 23 in the Amyloid β 1 - 28 Peptide

Lins

Soares

Ferreira

et al. 1999

Zeitschrift Für Naturforschung C

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The water accessibilities to aspartyl residues at positions 7 and 23 in the amyloid ß 1 -2 8 peptide associated with Alzheim er's Disease have been calculated using different techniques. These accessibilities of water were compared to those of the succinimidyl residues (SUC) replacing the aspartyl ones (ASP). It has been possible to ascertain that these modifications (A SP -»• SUC) lead to a significant increase in the water accessibility to the backbone and a-carbon atom of the SUC7 and SUC23 residues. It is suggested that the spontaneous trans formation of ASP -> SUC might lead to an increase of the racemization rates due to the higher accessibility of water at these sites. It is also proposed that the behavior of the adjacent residues in the selectivity of the racemization is to control the water accessibility at the reactive residue.

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Solution Structure of Residues 1-28 of the Amyloid .beta.-Peptide

Cited by 148 publications

References 87 publications

Nicotine Inhibits Amyloid Formation by the β-Peptide

Nicotine Inhibits Amyloid Formation by the β-Peptide

Alzheimer's Aβ40 Studied by NMR at Low pH Reveals That Sodium 4,4-Dimethyl-4-silapentane-1-sulfonate (DSS) Binds and Promotes β-Ball Oligomerization

Solvent Accessibility to Aspartyl and Succinimidyl Residues at Positions 7 and 23 in the Amyloid β 1 - 28 Peptide

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