Document Type
Article
Publication Date
10-16-2008
Abstract
Hepatitis C virus is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma infecting more than 170 million people. Hepatitis C virus envelope 2 glycoprotein (E2) binds several cell‐surface molecules that act as receptor candidates mediating hepatitis C virus entry into hepatocytes. Peptides derived from human lactoferrin have been shown to bind hepatitis C virus‐E2 protein thereby preventing hepatitis C virus entry in cultured hepatocytes. In this study, starting from a 33‐residue human lactoferrin‐derived peptide, a number of biotin‐linked α‐peptides were synthesized and investigated for their E2 protein binding activity. E2 protein from hepatitis C virus genotype 1b was expressed in 293 human embrionic kidney cells and purified using affinity chromatography. A biotin‐streptavidin based binding assay was developed to determine the binding affinity of the synthetic peptides for E2 protein. Two of the peptides bound E2 specifically with submicromolar to low micromolar affinity [equilibrium dissociation constant (Kd) of 0.569 and 28.8 μm]. Further, these two peptides had the highest helical content in solution as observed by circular dichroism spectroscopy, suggesting that binding affinity increases with increase in helicity. These results have provided new lead peptides for future investigations of hepatitis C virus entry inhibitors that may provide an interesting approach to prevent hepatitis C virus infectivity.
Recommended Citation
Beleid R, Douglas D, Kneteman N, Kaur K. Helical peptides derived from lactoferrin bind hepatitis C virus envelope protein E2. Chem. Biol. Drug Des. 2008;72(5):436-443. doi: 10.1111/j.1747-0285.2008.00715.x
Copyright
Wiley
Included in
Amino Acids, Peptides, and Proteins Commons, Medicinal and Pharmaceutical Chemistry Commons, Other Pharmacy and Pharmaceutical Sciences Commons, Virus Diseases Commons, Viruses Commons
Comments
This is the accepted version of the following article:
Beleid R, Douglas D, Kneteman N, Kaur K. Helical peptides derived from lactoferrin bind hepatitis C virus envelope protein E2. Chem. Biol. Drug Des. 2008;72(5):436-443.
which has been published in final form at DOI: 10.1111/j.1747-0285.2008.00715.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.