{
  "id": 4226531,
  "title": "Quantifying the binding affinity of a pharmacological chaperone to transient unfolded states of a normally folded protein",
  "url": "https://urgent.news/2026/08/28/quantifying-the-binding-affinity-of-a-pharmacological-chaperone-to",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-08-28T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.27.747683v1?rss=1"
  },
  "original_language": "en",
  "account": "The binding affinity of a pharmacological chaperone, pentosan polysulfate (PPS), to transiently unfolded states of a normally folded protein, the prion protein (PrP), has been quantified. Single-molecule force spectroscopy was employed to unfold individual PrP molecules without disrupting solution conditions, allowing observation of PPS interactions with unfolded states. The study focused on the bank vole prion protein (BvPrP) and found that PPS stabilized certain partially unfolded intermediates as well as the fully unfolded state of BvPrP. Strikingly, the tendency for PPS to bind unfolded states rather than the native folded state increased as the PPS concentration decreased, indicating a higher affinity for unfolded states. By comparing the relative amount of binding to unfolded versus folded states, researchers estimated that PPS bound roughly 100 times more tightly to unfolded states compared to the native PrP state. These findings emphasize the crucial role of unfolded states in prion misfolding and propagation, and demonstrate a method for estimating binding affinity to transient, unstable protein states.",
  "summary": "Binding of ligands to partially or fully unfolded proteins can play a key role in the mechanism of cellular and pharmacological chaperones, facilitating proper folding. However, it is challenging to quantify the binding affinity of ligands for unfolded states in a protein that is normally folded, as the methods standardly used to destabilize the native fold also affect ligand binding. We used…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}