The conformational restriction of synthetic vaccines for malaria

A. C. Satterthwait, L. C. Chiang, T. Arrhenius, E. Cabezas, F. Zavala, H. J. Dyson, P. E. Wright, R. A. Lerner

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


The effectiveness of synthetic vaccines is dependent upon the chance event that antibodies formed against largely disordered peptides can bind native protein surfaces which are often ordered. To improve on this situation, new methods are being developed for the conformational restriction of synthetic peptides. Cognate peptide sequences often form predictable secondary structures in proteins characterized by distinct hydrogen-bonding patterns. These weak hydrogen bonds have now been replaced with covalent mimics to conformationally restrict selected peptides to the Type 1 reverse turn and alpha helix. Potential uses for this chemistry are discussed in the context of malaria vaccines. The peptide component of a Plasmodium falciparum sporozoite vaccine, acetyl-(ASN-ALA-ASN-RPO)3-NH2 has been conformationally analysed using two-dimensional nuclear magnetic resonance spectroscopy. These studies are consistent with the formation of transiently ordered turnlike structures which provide a guide for the design and synthesis of a conformationally restricted synthetic vaccine. To assess the effects of conformational restriction and chemical modification on the sporozoite vaccine, ASN side-chains were linked around proline with ethylene bridges. Polyclonal antibodies to this shaped peptide show a strong cross-reaction with living sporozoites.

Original languageEnglish (US)
Pages (from-to)17-25
Number of pages9
JournalBulletin of the World Health Organization
Issue numberSUPPL.
StatePublished - Dec 1 1990
Externally publishedYes

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health


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