engleski

AC-FFA-NH2 TRIPEPTIDE HYDROGELATOR AS A MODEL OF KLVFF BINDING SITE OF Aβ-PROTEIN

Numerous binding studies with Aβ-amyloid aggregates and short peptides with selected Aβ- protein sequence have pointed to the KLVFF fragment of the amyloid as the most probable binding site of small aromatic molecules. It was shown that the formation of Aβ-amyloids and the formation of gel fibers by the low molecular weight peptidic gelators share some common features. Series of tripeptide FFA derivatives was synthesized and tested for gelation of water and organic solvents. Only Ac-FFA-NH2 tripeptide exhibited gelation of water by self-assembly under physiological conditions. TEM of the Ac-FFA-NH2 hydrogel and the methanol/water gel showed the presence of straight fibers with relatively uniform diameters of around 30 nm. FTIR and NMR investigation pointed toward the cross-β structure type of hydrogen bonding of the tripeptide in the gel aggregates. Conjugated dyes (Thioflavine T and Congo Red) are commonly used to stain the plaques in histopathological studies. Fluorescence titration of Ac-FFA-NH2 aqueous solution bellow its minimal gelation concentration with Thioflavin T (ThT) showed increase of ThT emission with increased tripetide concentration and formation of the 1:1 complex with significant association constant. Similar results were obtained with other Aβ-binders. These studies are expected to show if such Aβ-inspired hydrogelator aggregates could serve as a minimalist model of the Aβ-KLVFF binding site and possibly reveal its precise interaction with known and new binding molecules.

Aβ-amyloid aggregates; Self-assembly; Hydrogel;

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