Chemistry, an Asian journal 2017 03 16() doi 10.1002/asia.201700058
The 39-amino acid peptide fragment derived from prostatic acidic phosphatase (PAP), PAP248-286, is secreted in large amount into human semen and form amyloid fibrils. The fibrils can capture HIV virions and increase the attachment of virions to target cells, so they are called semen-derived enhancer of virus infection (SEVI). Therefore, it is of significance to inhibit the formation of PAP248-286 amyloid fibrils. Herein, we have demonstrated that brazilin could effectively inhibit PAP248-286 aggregation. The inhibition effect increased with increasing brazilin concentration. Thioflavin T fluorescence assays and transmission electron microscopic observations proved that few fibrils formed when brazilin was present with PAP248-286 in an equimolar concentration. Circular dichroism spectra indicated that brazilin inhibited the secondary structural transitions from α-helix and random coils to β-sheet. Cytotoxicity assays showed that brazilin significantly reduced the fibrils cytotoxicity at 0.01 mmol/L. Isothermal titration calorimetry revealed that hydrophobic interaction was the main force for brazilin binding to PAP248-286 monomer (dissociation constant, 4.03 μmol/L), and brazilin binding affinity for its fibrils was at least three orders of magnitude lower than for the monomer. The results indicate that brazilin would be a potential small molecule agent against SEVI.