Controlling beta-amyloid oligomerization by the use of naphthalene sulfonates - Trapping low molecular weight oligomeric species

Controlling beta-amyloid oligomerization by the use of naphthalene sulfonates - Trapping low molecular weight oligomeric species

Autor Ferrao-Gonzales, A. D. Google Scholar
Robbs, B. K. Google Scholar
Moreau, V. H. Google Scholar
Ferreira, A. Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Almeida, FCL Google Scholar
Silva, J. L. Google Scholar
Foguel, D. Google Scholar
Valente, A. P. Google Scholar
Instituição Universidade Federal do Rio de Janeiro (UFRJ)
Universidade Federal de São Paulo (UNIFESP)
Resumo Aggregation of proteins and peptides has been shown to be responsible for several diseases known as amyloidoses, which include Alzheimer disease ( AD), prion diseases, among several others. AD is a neurodegenerative disorder caused primarily by the aggregation of beta-amyloid peptide (A beta). Here we describe the stabilization of small oligomers of A beta by the use of sulfonated hydrophobic molecules such as AMNS (1-amino-5-naphthalene sulfonate); 1,8-ANS (1-anilinonaphthalene-8-sulfonate) and bis-ANS (4,4'-dianilino1,1'-binaphthyl-5,5'-disulfonate). the experiments were performed with either A beta-1-42 or with A beta-13-23, a shorter version of A beta that is still able to form amyloid fibrils in vitro and contains amino acid residues 16 - 20, previously shown to be essential to peptide-peptide interaction and fibril formation. All sulfonated molecules tested were able to prevent A beta aggregation in a concentration dependent fashion in the following order of efficacy: 1,8ANS< AMNS< bis-ANS. Size exclusion chromatography revealed that in the presence of bis-ANS, A beta forms a heterogeneous population of low molecular weight species that proved to be toxic to cell cultures. Since the ANS compounds all have apolar rings and negative charges ( sulfonate groups), both hydrophobic and electrostatic interactions may contribute to interpeptide contacts that lead to aggregation. We also performed NMR experiments to investigate the structure of A beta-13-23 in SDSmicelles and found features of an alpha-helix from Lys(16) to Phe(20). H-1 TOCSY spectra of A beta-13 - 23 in the presence of AMNS displayed a chemical-shift dispersion quite similar to that observed in SDS, which suggests that in the presence of AMNS this peptide might adopt a conformation similar to that reported in the presence of SDS. Taken together, our studies provide evidence for the crucial role of small oligomers and their stabilization by sulfonate hydrophobic compounds.
Idioma Inglês
Data 2005-10-14
Publicado em Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 280, n. 41, p. 34747-34754, 2005.
ISSN 0021-9258 (Sherpa/Romeo, fator de impacto)
Editor Amer Soc Biochemistry Molecular Biology Inc
Extensão 34747-34754
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000232403900046

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