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.
Key Laboratory of Functional Polymer Materials of Ministry of Education, and Institute of Polymer Chemistry, Nankai University, and Collaborative Innovation Center of Chemical Science and Engineering , Tianjin 300071, China.
Jing
J
Liu
Wei
W
Wang
Qian
Q
Zhang
Saihui
S
Zhang
Zhi
Z
Yuan
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D018625:Microscopy, Atomic Force; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary
D016229:Amyloid beta-Peptides; D010455:Peptides