Planejamento e desenvolvimento de novos potenciais agentes anti-Alzheimer, com bas...
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Texto completo | |
Autor(es): Mostrar menos - |
Cavini, Italo A.
[1, 2]
;
Munte, Claudia E.
[1, 2]
;
Erlach, Markus Beck
[2]
;
van Groen, Thomas
[3]
;
Kadish, Inga
[3]
;
Zhang, Tao
[4, 5]
;
Ziehm, Tamar
[5]
;
Nagel-Steger, Luitgard
[4, 5]
;
Kutzsche, Janine
[5]
;
Kremer, Werner
[2]
;
Willbold, Dieter
[4, 5]
;
Kalbitzer, Hans Robert
[2]
Número total de Autores: 12
|
Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Phys Inst Sao Carlos, Sao Carlos, SP - Brazil
[2] Univ Regensburg, Inst Biophys & Phys Biochem, Univ Str 31, D-93053 Regensburg - Germany
[3] Univ Alabama Birmingham, Birmingham, AL 35294 - USA
[4] Heinrich Heine Univ Dusseldorf, Inst Phys Biol & BMFZ, D-40225 Dusseldorf - Germany
[5] Forschungszentrum Julich, Struct Biochem ICS 6, Inst Complex Syst, D-52425 Julich - Germany
Número total de Afiliações: 5
|
Tipo de documento: | Artigo Científico |
Fonte: | CHEMICAL COMMUNICATIONS; v. 54, n. 26, p. 3294-3297, APR 4 2018. |
Citações Web of Science: | 5 |
Resumo | |
Pressure can shift the polymer-monomer equilibrium of A beta, increasing pressure first leads to a release of A beta-monomers, surprisingly at pressures higher than 180 MPa repolymerization is induced. By high pressure NMR spectroscopy, differences of partial molar volumes Delta V-0 and compressibility factors Delta beta' of polymerization were determined at different temperatures. The D-enantiomeric peptides RD2 and RD2D3 bind to monomeric A beta with affinities substantially higher than those determined for fibril formation. By reducing the A beta concentration below the critical concentration for polymerization they inhibit the formation of toxic oligomers. Chemical shift perturbation allows the identification of the binding sites. The D-peptides are candidates for drugs preventing Alzheimer's disease. We show that RD2D3 has a positive effect on the cognitive behaviour of transgenic (APPSwDI) mice prone to Alzheimer's disease. The heterodimer complexes have a smaller Stokes radius than A beta alone indicating the recognition of a more compact conformation of A beta identified by high pressure NMR before. (AU) | |
Processo FAPESP: | 10/01362-5 - Interação de proteínas com modelos de microdomínios lipídicos e membranas biológicas |
Beneficiário: | Claudia Elisabeth Munte |
Linha de fomento: | Auxílio à Pesquisa - Regular |
Processo FAPESP: | 13/04433-9 - Estrutura e dinâmica de estados excitados raros do peptídeo beta-amilóide da Doença de Alzheimer estudadas por ressonância magnética nuclear de alta pressão |
Beneficiário: | Italo Augusto Cavini |
Linha de fomento: | Bolsas no Brasil - Doutorado Direto |