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Brazilin Inhibits Prostatic Acidic Phosphatase Fibrillogenesis and Decreases its Cytotoxicity
Author(s) -
Li Ming,
Dong Xiaoyan,
Liu Yang,
Sun Yan
Publication year - 2017
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201700058
Subject(s) - fibrillogenesis , isothermal titration calorimetry , chemistry , circular dichroism , fibril , cytotoxicity , dissociation constant , monomer , biophysics , thioflavin , peptide , prostatic acid phosphatase , biochemistry , amyloid (mycology) , stereochemistry , in vitro , acid phosphatase , enzyme , organic chemistry , biology , receptor , polymer , medicine , inorganic chemistry , disease , pathology , alzheimer's disease
Abstract A 39‐amino acid peptide fragment that is derived from prostatic acidic phosphatase (PAP), PAP 248–286 , is secreted in large amounts in human semen and forms amyloid fibrils. These fibrils can capture HIV virions and increase the attachment of virions to target cells; as such, they are called a “semen‐derived enhancer of virus infection” (SEVI). Therefore, the inhibition of the formation of PAP 248–286 amyloid fibrils is of great significance. Herein, we demonstrate that brazilin effectively inhibits PAP 248–286 aggregation. The inhibitory effect increases with increasing brazilin concentration. Thioflavin T fluorescence assays and TEM observations confirmed that a few fibrils formed when brazilin was present with PAP 248–286 in an equimolar concentration. Circular dichroism spectroscopy indicated that brazilin inhibited the secondary structural transitions from α‐helices and random coils into β‐sheets. Cytotoxicity assays showed that brazilin significantly decreased the cytotoxicity of the fibrils at 0.01 mmol L −1 . Isothermal titration calorimetry revealed that hydrophobic interactions were the main driving force for the binding of brazilin to the PAP 248–286 monomer (dissociation constant, 4.03 μmol L −1 ), and that the binding affinity of brazilin for the fibrils was at least three orders of magnitude lower than that for the monomer. These results indicate that brazilin holds great potential as a small‐molecule agent against SEVIs.