Abstract
Chronic HBV infection is the leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). Synthetic peptides derived from the N-terminus of the large HBV envelope protein (L-protein) have been shown to efficiently block HBV entry. Myr-HBVpreS/2-78, the parent compound of these drugs, inhibits human HBV infection in vitro and in vivo. An efficient synthesis is required, as these peptides constitute a novel class of anti HBV drugs. Consequently, the solid phase synthesis of the N-terminal 77 amino acids of the viral L-protein was studied in detail. The peptide was N-terminally myristoylated to resemble the natural, postranslationally modified protein. The synthesis was monitored using the Fmoc cleavage pattern of the solid phase synthesis on a standard peptide synthesizer and by LC-MS analyses of the arising side products. "Difficult sequences" in the positions 42-47 of the peptide sequence complicate the efficient synthesis of the 77-mer peptide HBVpreS/2-78. Attempts were undertaken to optimize the synthesis by heating, double coupling or the use of pseudoproline dipeptides. HPLC-MS analyses showed that the efficiency of the synthesis could be increased best by temperature elevation. This resulted in a higher purity of ...Continue Reading
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