The conformational restriction of synthetic peptides, including a malaria peptide, for use as immunogens

Philos Trans R Soc Lond B Biol Sci. 1989 Jun 12;323(1217):565-72. doi: 10.1098/rstb.1989.0036.

Abstract

A new strategy is advanced for the conformational restriction of peptidyl immunogens. Our approach is to replace putative amide-amide hydrogen bonds with covalent hydrogen-bond mimics. Because on average every other amino acid in a protein engages in this bond, the syntheses of diversely shaped peptides can be contemplated. Synthetic methods for introducing a potential hydrogen-bond mimic into a peptide with alpha-helical potential is reported and the structural consequences are discussed. The replacement of the hydrogen bond with a chemical link will modify as well as shape the peptide. To explore the consequences of these changes, a potential synthetic vaccine for malaria, the repeating tetrapeptide Asn-Pro-Asn-Ala, was conformationally restricted. Antibodies to the shaped malarial peptide showed a strong cross reaction with Plasmodium falciparum sporozoites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Protozoan / immunology
  • Antibody Formation
  • Antigens, Protozoan / immunology*
  • Hydrogen Bonding
  • Malaria / immunology
  • Molecular Sequence Data
  • Plasmodium falciparum / immunology
  • Protein Conformation
  • Vaccines*
  • Vaccines, Synthetic*

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Vaccines
  • Vaccines, Synthetic