The conformational restriction of synthetic peptides, including a malaria peptide, for use as immunogens.
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.
Satterthwait
A C
AC
Research Institute of Scripps Clinic, La Jolla, California 92037.
Arrhenius
T
T
Hagopian
R A
RA
Zavala
F
F
Nussenzweig
V
V
Lerner
R A
RA
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
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D014612:Vaccines; D014614:Vaccines, Synthetic