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Synthesis of the full-length hepatitis B virus core protein and its capsid formation.

Keisuke AokiShugo TsudaNaoko OgataMichiyo KataokaJumpei SasakiShinsuke InukiHiroaki OhnoKoichi WatashiTaku YoshiyaShinya Oishi
Published in: Organic & biomolecular chemistry (2024)
Chronic infection with hepatitis B virus (HBV) is a major cause of cirrhosis and liver cancer. Capsid assembly modulators can induce error-prone assembly of HBV core proteins to prevent the formation of infectious virions, representing promising candidates for treating chronic HBV infections. To explore novel capsid assembly modulators from unexplored mirror-image libraries of natural products, we have investigated the synthetic process of the HBV core protein for preparing the mirror-image target protein. In this report, the chemical synthesis of full-length HBV core protein (Cp183) containing an arginine-rich nucleic acid-binding domain at the C-terminus is presented. Sequential ligations using four peptide segments enabled the synthesis of Cp183 via convergent and C-to-N direction approaches. After refolding under appropriate conditions, followed by the addition of nucleic acid, the synthetic Cp183 assembled into capsid-like particles.
Keyphrases
  • hepatitis b virus
  • nucleic acid
  • liver failure
  • protein protein
  • small molecule
  • amino acid
  • binding protein