Computational and experimental studies on β-sheet breakers targeting Aβ1-40 fibrils.

ABSTRACT: In this work we present and compare the results of extensive molecular dynamics simulations of model systems comprising an Aβ1-40 peptide in water in interaction with short peptides (β-sheet breakers) mimicking the 17-21 region of the Aβ1-40 sequence. Various systems differing in the customized β-sheet breaker structure have been studied. Specifically we have considered three kinds of β-sheet breakers, namely Ac-LPFFD-NH2 and two variants thereof, one obtained by substituting the acetyl group with the sulfonic amino acid taurine (Tau-LPFFD-NH2) and a second novel one in which the aspartic acid is substituted by an asparagine (Ac-LPFFN-NH2). Thioflavin T fluorescence, circular dichroism, and mass spectrometry experiments have been performed indicating that β-sheet breakers are able to inhib

SUBMITTER: Minicozzi V 

PROVIDER: S-EPMC4036262 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature