Conformational restriction of peptidyl immunogens with covalent replacements for the hydrogen bond

Arnold C. Satterthwait, Thomas Arrhenius, Robert A. Hagopian, Fidel Zavala, Victor Nussenzweig, Richard A. Lerner

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

A new strategy for designing synthetic vaccines is presented. In this approach synthetic peptides are conformationally restricted by replacing putative hydrogen bonds with covalent mimics. The chemistry for substituting a hydrazone-ethane link (N-N=CH-CH2-CH2) for an (1 + 4)1 hydrogen bond in a pentapeptide with α-helical potential is reported. Chemically shaping peptides to mimic the three-dimensional surfaces of proteins may enhance their immunogenicity. To test this strategy, a potential synthetic vaccine for malaria, Cys-(Asn-Pro-Asn-Ala)3-NH2, was conformationally restricted by replacing putative hydrogen bonds between asparagine side chains with a covalent replacement, an ethylene bridge, to give first generation chemically shaped immunogens. Antibodies to one of the shaped malarial peptides show a strong reaction with living Plasmodium falciparum sporozoites, a form of malaria which infects hundreds of millions of people yearly.

Original languageEnglish (US)
Pages (from-to)99-103
Number of pages5
JournalVaccine
Volume6
Issue number2
DOIs
StatePublished - Apr 1988
Externally publishedYes

Keywords

  • Malaria
  • conformation
  • mimics
  • peptides
  • reverse turn
  • α-helix

ASJC Scopus subject areas

  • Molecular Medicine
  • General Immunology and Microbiology
  • General Veterinary
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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