Inhibitory effect of naphthoquinone-tryptophan hybrid towards aggregation of PAP F39 semen amyloid

Viswanathan Guru KrishnaKumar, Satabdee Mohapatra, Ashim Paul, Elad Arad, Raz Jelinek, Ehud Gazit, Daniel Segal

Research output: Contribution to journalArticlepeer-review

Abstract

PAP248–286, a 39 amino acid peptide fragment, derived from the prostatic acid phosphatase secreted in human semen, forms amyloid fibrils and facilitates the attachment of retroviruses to host cells that results in the enhancement of viral infection. Therefore, the inhibition of amyloid formation by PAP248–286 (termed PAP f39) may likely reduce HIV transmission in AIDS. In this study, we show that the naphthoquinone tryptophan (NQTrp) hybrid molecule significantly inhibited PAP f39 aggregation in vitro in a dose-dependent manner as observed from the ThT assay, ANS assay, and transmission electron microscopy imaging. We found that even at a sub-molar concentration of 20:1 [PAP f39:NQTrp], NQTrp could reduce >50% amyloid formation. NQTrp inhibition of PAP f39 aggregation resulted in non-toxic intermediate species as determined by the vesicle leakage assay. Isothermal titration calorimetry and molecular docking revealed that the binding of NQTrp and PAP f39 is spontaneous, and NQTrp predominantly interacts with the polar and charged residues of the peptide by forming hydrogen bonds and hydrophobic contacts with a strong binding energy. Collectively, these findings indicate that NQTrp holds significant potential as a small molecule inhibitor of semen amyloids.

Original languageEnglish
Article number3279
JournalMolecules
Volume23
Issue number12
DOIs
StatePublished - 11 Dec 2018

Keywords

  • Amyloid inhibition
  • NQTrp
  • PAP peptide
  • Polypeptide aggregation
  • Semen amyloids

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