C-Terminal PEG Blocks the Irreversible Step in β-Amyloid(10-35) Fibrillogenesis

Burkoth, Timothy S.; Benzinger, Tammie L.S.; Jones, David N. M.; Hallenga, Klaas; Meredith, Stephen C.; Lynn, David G.

doi:10.1021/ja980566b

Cited by 152 publications

(172 citation statements)

References 20 publications

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“…At the end of this procedure, a precipitate had formed, which was entirely fibrillar by electron microscopy; that is, no amorphous precipitate was visible. Furthermore, as published elsewhere (41), the fibrils could be stained by Congo Red stain, and when viewed under doubly polarized light, they displayed classical apple-green birefringence. The suspension of fibrils then was flash-frozen, lyophilized, and stored at Ϫ20°C for solid-state NMR studies.…”

Section: Methodssupporting

confidence: 63%

Propagating structure of Alzheimer’s β-amyloid _(10–35) is parallel β-sheet with residues in exact register

Benzinger

Gregory

Burkoth

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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413

525

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The pathognomonic plaques of Alzheimer's disease are composed primarily of the 39-to 43-aa ␤-amyloid (A␤) peptide. Crosslinking of A␤ peptides by tissue transglutaminase (tTg) indicates that Gln 15 of one peptide is proximate to Lys 16 of another in aggregated A␤. Here we report how the fibril structure is resolved by mapping interstrand distances in this core region of the A␤ peptide chain with solid-state NMR. Isotopic substitution provides the source points for measuring distances in aggregated A␤. Peptides containing a single carbonyl 13 C label at Gln 15 , Lys 16 , Leu 17 , or Val 18 were synthesized and evaluated by NMR dipolar recoupling methods for the measurement of interpeptide distances to a resolution of 0.2 Å. Analysis of these data establish that this central core of A␤ consists of a parallel ␤-sheet structure in which identical residues on adjacent chains are aligned directly, i.e., in register. Our data, in conjunction with existing structural data, establish that the A␤ fibril is a hydrogen-bonded, parallel ␤-sheet defining the long axis of the A␤ fibril propagation.

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Section: Methodssupporting

confidence: 63%

Propagating structure of Alzheimer’s β-amyloid _(10–35) is parallel β-sheet with residues in exact register

Benzinger

Gregory

Burkoth

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

413

525

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“…Concretely, the technique consisted in using polystyrene (PS) beads loaded with amino-terminated poly(ethylene glycol) (PEG) through an acid labile benzyl-ether linker [40][41][42][43][44]. Subsequently, SPPS was successfully conducted with high efficiency from PEG according to the so-called "divergent approach" or alternatively a selected pre-formed peptide was chemically linked to the synthetic polymer chain giving rise to the "convergent approach".…”

Section: Solid-phase Peptide Synthesis Preparation Of Peptide-synthementioning

confidence: 99%

Hybrid Block Copolymers Constituted by Peptides and Synthetic Polymers: An Overview of Synthetic Approaches, Supramolecular Behavior and Potential Applications

Morell

Puiggalı́

2013

Polymers

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Hybrid block copolymers based on peptides and synthetic polymers, displaying different types of topologies, offer new possibilities to integrate the properties and functions of biomacromolecules and synthetic polymers in a single hybrid material. This review provides a current status report of the field concerning peptide-synthetic polymer hybrids. The first section is focused on the different synthetic approaches that have been used within the last three years for the preparation of peptide-polymer hybrids having different topologies. In the last two sections, the attractive properties, displayed in solution or in the solid state, together with the potential applications of this type of macromolecules or supramolecular systems are highlighted.

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“…These supports contain chain-end functionalised 30 PEO and are used in the same manner as SPPS, with the exception that, following cleavage from the resin, the final product contains a PEO block. 93,94 Although this approach produces well-defined polymer-peptide conjugates with simple purification strategies, pre-loaded resins are only 35 currently available with PEO anchored to the surface and the range of available molecular weights is limited. This is where we must turn to different approaches to afford hybrid peptide conjugates with a wider variety of molecular weight, chemical composition and molecular structure.…”

Section: Divergent Peptide Incorporationmentioning

confidence: 99%

Peptide conjugate hydrogelators

2010

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5Molecular gelators are currently receiving a great deal of attention. These are small molecules which, under the appropriate conditions, assemble in solution to, in the majority of cases, give long fibrillar structures which entangle to form a three-dimensional network. This immobilises the solvent, resulting in a gel. Such gelators have potential application in a number of important areas from drug delivery to tissue engineering. Recently, the use of peptide-conjugates has become 10 prevalent with oligopeptides (from as short as two amino acids in length) co njugated to a polymer, alkyl chain or aromatic group such as naphthalene or fluorenylmethoxycarbonyl (Fmoc) being shown to be effective molecular gelators. The field of gelation is extremely large; here we will focus our attention on the use of these peptide-conjugates as molecular hydrogelators.

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C-Terminal PEG Blocks the Irreversible Step in β-Amyloid(10-35) Fibrillogenesis

Cited by 152 publications

References 20 publications

Propagating structure of Alzheimer’s β-amyloid _(10–35) is parallel β-sheet with residues in exact register

Propagating structure of Alzheimer’s β-amyloid _(10–35) is parallel β-sheet with residues in exact register

Hybrid Block Copolymers Constituted by Peptides and Synthetic Polymers: An Overview of Synthetic Approaches, Supramolecular Behavior and Potential Applications

Peptide conjugate hydrogelators

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C-Terminal PEG Blocks the Irreversible Step in β-Amyloid(10-35) Fibrillogenesis

Cited by 152 publications

References 20 publications

Propagating structure of Alzheimer’s β-amyloid (10–35) is parallel β-sheet with residues in exact register

Propagating structure of Alzheimer’s β-amyloid (10–35) is parallel β-sheet with residues in exact register

Hybrid Block Copolymers Constituted by Peptides and Synthetic Polymers: An Overview of Synthetic Approaches, Supramolecular Behavior and Potential Applications

Peptide conjugate hydrogelators

Contact Info

Product

Resources

About

Propagating structure of Alzheimer’s β-amyloid _(10–35) is parallel β-sheet with residues in exact register

Propagating structure of Alzheimer’s β-amyloid _(10–35) is parallel β-sheet with residues in exact register