Solid-phase synthesis of the lipopeptide Myr-HBVpreS/2-78, a hepatitis B virus entry inhibitor.

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Alexa SchieckWalter Mier

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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Citations

Apr 23, 2013·Molecular Pharmaceutics·Thomas MüllerWalter Mier
Dec 27, 2011·Expert Opinion on Emerging Drugs·Natravis Cox, Hans Tillmann
Feb 3, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Davor SlijepcevicStan F J van de Graaf
Jan 8, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alexa SchieckWalter Mier
Apr 7, 2016·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·P UhlG Fricker
Oct 26, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Michael ReinwarthOlga Avrutina
Aug 1, 2019·Current Drug Targets·Bing-Yi ZhangXiao-Ping Yu
Feb 19, 2021·Journal of Viral Hepatitis·Dongliang ChengWei Wu

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Methods Mentioned

BETA
aminoacylation
acetylations
acetylation

Software Mentioned

Peptide Companion

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