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Titolo:
SELECTIVE-INHIBITION OF A-BETA FIBRIL FORMATION
Autore:
WOOD SJ; MACKENZIE L; MALEEFF B; HURLE MR; WETZEL R;
Indirizzi:
1732 HAMILTON DR PHOENIXVILLE PA 19460 SMITHKLINE BEECHAM PHARMACEUT,DEPT TOXICOL KING OF PRUSSIA PA 19406 SMITHKLINE BEECHAM PHARMACEUT,DEPT BIOMOL CHEM KING OF PRUSSIA PA 19406 SMITHKLINE BEECHAM PHARMACEUT,DEPT MACROMOLEC SCI KING OF PRUSSIA PA 19406
Titolo Testata:
The Journal of biological chemistry
fascicolo: 8, volume: 271, anno: 1996,
pagine: 4086 - 4092
SICI:
0021-9258(1996)271:8<4086:SOAFF>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALZHEIMERS-DISEASE; CIRCULAR-DICHROISM; AMYLOID PROTEIN; PEPTIDES; BINDING; TRANSTHYRETIN; CONFORMATION; INVITRO;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
S.J. Wood et al., "SELECTIVE-INHIBITION OF A-BETA FIBRIL FORMATION", The Journal of biological chemistry, 271(8), 1996, pp. 4086-4092

Abstract

We describe here an inhibitor of in vitro fibril formation, hexadecyl-N-methylpiperidinium (HMP) bromide, which is selective for the Alzheimer's disease peptide A beta. At 10 mu M, its IC50 for inhibiting A beta aggregation at pH 5.8, HMP bromide does not inhibit fibril formation by other amyloidogenic polypeptides nor does it affect the folding stability of the beta-sheet-rich immunoglobulin V-L domain REI, In addition, small structural modifications of HMP bromide reduce or eliminate its ability to inhibit pH 5.8 aggregation of A beta, These indications of specificity, plus the ability of the molecule to inhibit A beta aggregation at concentrations almost an order of magnitude below its critical micelle concentration, suggest a mechanism of inhibition otherthan micellar solubilization of A beta. HMP bromide is required in approximately a 1:1 stoichiometry for effective inhibition at pH 5.8. Although stoichiometric amounts of HMP bromide with respect to total A beta inhibit A beta fibril formation at pH 7.4, the molecule is incapable, at lower concentrations, of blocking the seeding of fibril formation by small amounts of added A beta fibrils, The results suggest the existence of a binding surface on A beta capable of binding amphipathicmolecules such as HMP bromide and which, when occupied, precludes assembly of A beta into amyloid fibrils. Molecules that bind to this sitewith high specificity may prove to be useful therapeutic agents for preventing or retarding the cerebral amyloid plaque formation implicated in Alzheimer's disease pathology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 18:20:03