Solid phase synthesis of potential antigenic peptides and new lipopeptides of hepatitis B virus

Abstract

Peptides belonging to the envelope protein of HBV [Tyr¹⁴⁸]S(139–148) and preS(120–145) have been synthesized using the continuous-flow fluoren-9-ylmethoxycarbonyl (Fmoc)-polyamide solid phase methodology. Furthermore, the synthesis of a new series of hydrophobic derivatives involving N^α-acylation of both peptides with stearic and cholanic acid as well as the introduction of the synthetic B-cell and macrophage activator Pam₃-Cys-Ser-Ser is also described. Benzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate (PyBOP) and benzotriazol-1-yloxytris(dimethylamino) phosphonium hexafluorophosphate (BOP) proved to be convenient reagents to promote the coupling of these lipid moieties to peptides attached to Kieselguhr-supported polyacrylamide resins. Some synthetic aspects concerning reaction conditions and the use of different scavengers at the cleavage stage are discussed. Finally, a cyclic derivative of the S peptide was obtained through a disulphide bond formation.