Study on the efficiency and interaction mechanism of a decapeptide inhibitor of β-amyloid aggregation.

This paper reports an active decapeptide inhibitor (RR: RYYAAFFARR) of β-amyloid (Aβ(1-40)) aggregation. Traditional inhibitors target the hydrophobic core of Aβ (Aβ(16-20)) and were designed based on the single hydrophobic interaction. RR was designed to target an extended region (Aβ(11-23)), which contains three important regions of Aβ(1-40). RR exhibits stronger binding affinity for Aβ(1-40) (K(D) = 1.10 μM) than the known β-sheet breaker LPFFD (K(D) = 156 μM). Our study shows that RR inhibited the fibrillation of Aβ(1-40) by nearly 75% at an equimolar concentration, and that a 1:4 ratio of Aβ(1-40)/ RR almost completely inhibited fibrillation. The interaction mechanism was also investigated by changing the ionic strength or the structure of RR. The results revealed that RR binds to Aβ(1-40) because of its strong affinity for Aβ(11-23), which is mainly driven by hydrophobic and electrostatic interactions and hydrogen bonding.