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

• Published in: Organic & biomolecular chemistry Vol. 22; no. 11; pp. 2218 - 2225
• Main Authors: Aoki, Keisuke, Tsuda, Shugo, Ogata, Naoko, Kataoka, Michiyo, Sasaki, Jumpei, Inuki, Shinsuke, Ohno, Hiroaki, Watashi, Koichi, Yoshiya, Taku, Oishi, Shinya
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 13.03.2024
• Subjects: Antiviral Agents - metabolism; Assembly; C-Terminus; Capsid - chemistry; Capsid Proteins - metabolism; Chemical synthesis; Chronic infection; Cirrhosis; Core protein; Hepatitis; Hepatitis B; Hepatitis B - metabolism; Hepatitis B virus; Humans; Liver cancer; Modulators; Natural products; Nucleic Acids; Proteins; Viral Core Proteins - analysis; Viral Core Proteins - chemistry; Viral Core Proteins - metabolism; Virions; Virus Replication
• ISSN: 1477-0520; 1477-0539; 1477-0539
• DOI: 10.1039/d3ob02099a

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. Protocols for chemical synthesis and in vitro assembly of the hepatitis B virus full-length core protein (Cp183) were investigated.