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Interaction between amyloid beta peptide and an aggregation blocker peptide mimicking islet amyloid polypeptide.


ABSTRACT: Assembly of amyloid-beta peptide (A?) into cytotoxic oligomeric and fibrillar aggregates is believed to be a major pathologic event in Alzheimer's disease (AD) and interfering with A? aggregation is an important strategy in the development of novel therapeutic approaches. Prior studies have shown that the double N-methylated analogue of islet amyloid polypeptide (IAPP) IAPP-GI, which is a conformationally constrained IAPP analogue mimicking a non-amyloidogenic IAPP conformation, is capable of blocking cytotoxic self-assembly of A?. Here we investigate the interaction of IAPP-GI with A?40 and A?42 using NMR spectroscopy. The most pronounced NMR chemical shift changes were observed for residues 13-20, while residues 7-9, 15-16 as well as the C-terminal half of A?--that is both regions of the A? sequence that are converted into ?-strands in amyloid fibrils--were less accessible to solvent in the presence of IAPP-GI. At the same time, interaction of IAPP-GI with A? resulted in a concentration-dependent co-aggregation of A? and IAPP-GI that was enhanced for the more aggregation prone A?42 peptide. On the basis of the reduced toxicity of the A? peptide in the presence of IAPP-GI, our data are consistent with the suggestion that IAPP-GI redirects A? into nontoxic "off-pathway" aggregates.

SUBMITTER: Rezaei-Ghaleh N 

PROVIDER: S-EPMC3102090 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Interaction between amyloid beta peptide and an aggregation blocker peptide mimicking islet amyloid polypeptide.

Rezaei-Ghaleh Nasrollah N   Andreetto Erika E   Yan Li-Mei LM   Kapurniotu Aphrodite A   Zweckstetter Markus M  

PloS one 20110525 5


Assembly of amyloid-beta peptide (Aβ) into cytotoxic oligomeric and fibrillar aggregates is believed to be a major pathologic event in Alzheimer's disease (AD) and interfering with Aβ aggregation is an important strategy in the development of novel therapeutic approaches. Prior studies have shown that the double N-methylated analogue of islet amyloid polypeptide (IAPP) IAPP-GI, which is a conformationally constrained IAPP analogue mimicking a non-amyloidogenic IAPP conformation, is capable of bl  ...[more]

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