Myrcludex B (Bulevirtide) His6-tagged

Myrcludex B (Bulevirtide), His6-tagged is a myristoylated 47-residue lipopeptide corresponding to residues 2–48 of the preS1 domain of the hepatitis B virus (HBV) large surface protein, extended at the C-terminus with a hexahistidine tag for immobilization and detection.

Background

Hepatitis B and hepatitis D virus entry into hepatocytes begins with low-affinity attachment to cell-surface heparan sulfate proteoglycans, followed by high-affinity engagement of NTCP by the myristoylated preS1 domain of the viral large surface protein. Blocking this step prevents productive infection, and the preS1 2–48 lipopeptide is the prototype of this class of entry inhibitors. The unmodified parent peptide, bulevirtide (formerly Myrcludex B), is a first-in-class entry inhibitor that received conditional marketing authorization in the European Economic Area and the United Kingdom and, in May 2026, accelerated approval in the United States for chronic hepatitis delta infection on the basis of the phase 3 MYR301 study.

A cryo-EM structure of myristoylated preS1 2–48 bound to human NTCP shows the folded N-terminal half of the peptide inserting deeply into the outward-facing tunnel of the transporter while the C-terminal half makes extensive contacts across the extracellular surface — an induced-fit binding mode that explains the high affinity of the interaction and provides a template for structure-guided entry-inhibitor design. Consistent with its site of action, the peptide also inhibits NTCP-mediated bile salt uptake, with a reported IC₅₀ of 195 nM for taurocholate transport in NTCP-expressing cells. Myristoylation is strictly required: non-myristoylated preS1 peptides show only marginal activity in HBV infection assays, and truncation studies identified Myr 2–48 as the most inhibitory of the preS1 fragments tested.

Why the His6 tag

The hexahistidine extension lets the peptide be captured on Ni-NTA or cobalt resin and on Ni-NTA-coated plates and biosensor surfaces, and detected with anti-His antibodies, without consuming the N-terminal myristoyl group that the NTCP interaction depends on. Typical uses include oriented immobilization for pull-down and co-precipitation of NTCP and candidate co-receptors, surface-plasmon-resonance and ELISA-format binding measurements, affinity enrichment of peptide–receptor complexes, and controls alongside biotinylated or fluorophore-labeled preS1 probes in cell-binding and competition assays.

Related modifications available

LifeTein synthesizes this peptide to order and can supply matched variants for assay development: non-myristoylated control, scrambled and Ala-substituted negative controls, deletion of residues 11–15, N- or C-terminal biotin, FITC/TAMRA/Alexa-type fluorophores, PEG spacers, and C-terminal amide in place of the free acid. Custom tag length and placement, and alternative lipid chains, are also available. Peptides are made in our New Jersey facility, with 3–5 days for crude material and about 6 days for purified 1–4 mg.

References

1. Asami J, Park JH, Nomura Y, et al. Structural basis of hepatitis B virus receptor binding. Nat Struct Mol Biol. 2024;31:447–454.
2. Liu H, Zakrzewicz D, Nosol K, et al. Structure of hepatitis B/D antiviral drug bulevirtide bound to its receptor protein NTCP. Nat Commun. 2024;15:2476.
3. Haag M, Hofmann U, Mürdter TE, et al. Quantitative bile acid profiling and intact plasma quantification of the large therapeutic lipopeptide bulevirtide. Anal Bioanal Chem. 2021.
4. Hinuma S, Kuroda S. Binding of hepatitis B virus pre-S1 domain-derived synthetic myristoylated peptide to scavenger receptor class B type 1. Viruses. 2022;14(2):227.

For research use only. Not intended for diagnostic or therapeutic procedures or for human or animal consumption.