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: A C Satterthwait, T Arrhenius, R A Hagopian, F Zavala, V Nussenzweig, R A Lerner
• Journal: Philosophical transactions of the Royal Society of London. Series B, Biological sciences (Philos Trans R Soc Lond B Biol Sci) Vol. 323 Issue 1217 Pg. 565-72 (Jun 12 1989) ISSN: 0962-8436 [Print] England
• PMID: 2569211 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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