title: The conformational restriction of synthetic peptides, including a malaria peptide, for use as immunogens.
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.
authors.affiliation: Research Institute of Scripps Clinic, La Jolla, California 92037.
authors.forename: A C
authors.initials: AC
authors.lastname: Satterthwait
authors.forename: T
authors.initials: T
authors.lastname: Arrhenius
authors.forename: R A
authors.initials: RA
authors.lastname: Hagopian
authors.forename: F
authors.initials: F
authors.lastname: Zavala
authors.forename: V
authors.initials: V
authors.lastname: Nussenzweig
authors.forename: R A
authors.initials: RA
authors.lastname: Lerner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000276:immunology*; D006860:Hydrogen Bonding; D008288:Malaria / Q000276:immunology; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology; D011487:Protein Conformation; D014612:Vaccines; D014614:Vaccines, Synthetic
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D014612:Vaccines; D014614:Vaccines, Synthetic