Synthesis and in vitro stability of peptide derivatives for hepatitis B virus infection

Abstract

Previous studies reported that hepatitis B virus (HBV) enters into hepatocytes via interaction with one of membrane proteins. Therefore, viral infection can be inhibited by blocking the interaction between virus and the membrane protein, and peptides can be designed for the inhibition. However, peptides are susceptible to proteolysis in physiological conditions resulting in unsatisfactory metabolic stability and short serum half-life which made peptides difficult to be used as drugs. Here, we improved the in vitro stability of peptides by several modifications. Modified peptide derivatives showed significantly increased stability in human serum and rat whole blood while retaining their in vitro inhibitory activity. These results provide strategies for enhancing the proteolytic stability of peptides considered as drug candidates.