Interaction of PiB-derivative metal complexes with beta-amyloid peptides: selective recognition of the aggregated forms.
Chemistry
; 21(14): 5413-22, 2015 Mar 27.
Article
em En
| MEDLINE
| ID: mdl-25712142
ABSTRACT
Metal complexes are increasingly explored as imaging probes in amyloid peptide related pathologies. We report the first detailed study on the mechanism of interaction between a metal complex and both the monomer and the aggregated form of Aß1-40 peptide. We have studied lanthanide(III) chelates of two PiB-derivative ligands (PiB=Pittsburgh compound B), L(1) and L(2), differing in the length of the spacer between the metal-complexing DO3A macrocycle (DO3A=1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid) and the peptide-recognition PiB moiety. Surface plasmon resonance (SPR) and saturation transfer difference (STD) NMR spectroscopy revealed that they both bind to aggregated Aß1-40 (KD =67-160â
µM), primarily through the benzothiazole unit. HSQCâ
NMR spectroscopy on the (15) N-labeled, monomer Aß1-40 peptide indicates nonsignificant interaction with monomeric Aß. Time-dependent circular dichroism (CD), dynamic light scattering (DLS), and TEM investigations of the secondary structure and of the aggregation of Aß1-40 in the presence of increasing amounts of the metal complexes provide coherent data showing that, despite their structural similarity, the two complexes affect Aß fibril formation distinctly. Whereas GdL(1), at higher concentrations, stabilizes ß-sheets, GdL(2) prevents aggregation by promoting α-helical structures. These results give insight into the behavior of amyloid-targeted metal complexes in general and contribute to a more rational design of metal-based diagnostic and therapeutic agents for amyloid- associated pathologies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Tiazóis
/
Peptídeos beta-Amiloides
/
Elementos da Série dos Lantanídeos
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Complexos de Coordenação
/
Agregados Proteicos
/
Compostos de Anilina
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Chemistry
Assunto da revista:
QUIMICA
Ano de publicação:
2015
Tipo de documento:
Article