Open AccessSulfonated Compounds Bind with Prostatic Acid Phosphatase (PAP 248–286 ) to Inhibit the Formation of Amyloid Fibrils
Author(s) -
Zhang Tingting,
Yang Haikui,
Yang Zichao,
Tan Suiyi,
Jin Jiabin,
Liu Shuwen,
Zhang Jiajie
Publication year - 2018
Publication title -
chemistryopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.644
H-Index - 29
ISSN - 2191-1363
DOI - 10.1002/open.201800041
Subject(s) - prostatic acid phosphatase , chemistry , peptide , fibril , amyloid (mycology) , surface plasmon resonance , hydrogen bond , sulfonate , biophysics , hydrophobic effect , small molecule , molecule , biochemistry , combinatorial chemistry , acid phosphatase , nanoparticle , enzyme , biology , organic chemistry , nanotechnology , materials science , inorganic chemistry , sodium
The peptide segment of prostatic acid phosphatase (PAP 248–286 ) aggregates to form SEVI (semen‐derived enhancer of virus infection) amyloid fibrils. These are characteristic seminal amyloids that have the ability to promote the effect of HIV infection. In this paper, we explore the binding of sulfonated compounds with PAP 248–286 through an in silico study. Three derivatives of suramin, NF110, NF279, and NF340, are selected. All of these sulfonated molecules bind to PAP 248–286 and alter the conformation of the peptide, even though they have various structures, sizes, and configurations. The compounds bind with PAP 248–286 through multiple interactions, such as hydrogen‐bonding interactions, hydrophobic interactions, π–π stacking interactions, and electrostatic interactions. However, NF110, which has an X‐shaped configuration, has the highest binding affinity of the three derivatives investigated. We also perform surface plasmon resonance and a Congo red assay to validate the results. The interactions between PAP 248–286 and the sulfonated compounds are proposed to depend on the orientations of the sulfonate groups and the specific configurations of the compounds instead of the number of sulfonate groups. NF110 molecules occupy the exposed binding sites of PAP 248–286 , blocking interactions between the peptides. Therefore, these compounds are important in inhibiting the aggregation of PAP 248–286 . Herein, we provide useful information to develop new efficient microbicides to antagonize seminal amyloid fibrils and to block HIV transmission.