{
  "id": 5463580,
  "title": "Enhancing the Identification of NHS Ester-Mediated Lysine-Cysteine Cross-Linking via Reduced Trypsin Digestion Time",
  "url": "https://urgent.news/2026/09/03/enhancing-the-identification-of-nhs-ester-mediated-lysine-cysteine",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-09-03T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748724v1?rss=1"
  },
  "original_language": "en",
  "account": "A study has revealed that NHS ester-mediated lysine-cysteine (K-C) cross-linking can be reliably identified in chemical cross-linking mass spectrometry (XL-MS) despite previous concerns about the stability of these bonds. By optimizing the XL-MS workflow, researchers have demonstrated that K-C cross-links, which were once considered labile, constitute 23% to 59% of total detected cross-links in four model proteins. These cross-links have C-C distances ranging from 12 to 40 angstroms, and 60% of them meet theoretical linker constraints, proving their reliability comparable to canonical lysine-lysine (K-K) cross-link sites. Furthermore, software validation and comparison with another heterobifunctional K-C cross-linker, GMBS, showed that the optimized workflow captures approximately 40% of GMBS-identified K-C cross-linked sites. This advancement significantly expands the practical use of NHS esters and facilitates simultaneous acquisition of K-K and K-C distance constraints, thereby enhancing protein structural characterization.",
  "summary": "Abstract Chemical cross-linking mass spectrometry (XL-MS) is a powerful technique for elucidating protein structures and interactions, with NHS ester-based cross-linkers being the most widely used. Traditionally, NHS esters are considered highly specific for primary amines; although their reactivity toward cysteine thiols has been reported, it has not been systematically characterized in XL-MS…",
  "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."
}