Synthesis, conformation, and immunogenicity of monosaccharide-centered multivalent HIV-1 gp41 peptides containing the sequence of DP178.
Several monosaccharide-centered multivalent HIV-1 gp41 peptides containing the sequence of DP178 were synthesized. Conformational studies showed that multivalent assembly enhanced the alpha-helical content of the peptide. Therefore, 2-, 3-, or 4-alpha-helix bundles of peptide DP178 could be obtained by assembling the peptide on a suitable bi-, tri-, or tetravalent template. Immunization studies indicated that while peptide DP178 alone was poorly immunogenic, the tetravalent peptide MVP-1 raised high titers of antibodies in mice that recognize not only peptide DP178 but also the native HIV-1 glycoprotein gp41, even in the absence of a carrier protein or adjuvant. The study suggests that carbohydrate-centered multivalent peptides provide not only a model for mimicking protein alpha-helix-bundle structure, but also an effective immunogen for raising high-titer antibodies against HIV-1 envelope glycoprotein gp41.
Ni
Jiahong
J
Institute of Human Virology, University of Maryland Biotechnology Institute, University of Maryland, 725 Lombard Street, Baltimore, MD 21201, USA.
Powell
Robert
R
Baskakov
Ilia V
IV
DeVico
Anthony
A
Lewis
George K
GK
Wang
Lai-Xi
LX
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002942:Circular Dichroism; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009005:Monosaccharides / Q000138:chemical synthesis / Q000737:chemistry*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology*; D011487:Protein Conformation
D000914:Antibodies, Viral; D015700:HIV Envelope Protein gp41; D009005:Monosaccharides; D010446:Peptide Fragments; D000077560:Enfuvirtide