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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Jan 4;91(1):380–384. doi: 10.1073/pnas.91.1.380

Topography of a binding site for small amnestic peptides deduced from structure-activity studies: relation to amnestic effect of amyloid beta protein.

J F Flood 1, E Roberts 1, M A Sherman 1, B E Kaplan 1, J E Morley 1
PMCID: PMC42951  PMID: 8278398

Abstract

Four peptides homologous to amyloid beta protein containing the Val-Phe-Phe (VFF) sequence administered intracerebroventricularly after training caused amnesia for footshock active avoidance training in mice. Results with VFF and other peptides containing VFF or portions thereof were used to generate a topographic map for a hypothetical binding surface for amnestic peptides, termed Z. Effects on retention of footshock active avoidance training were rationalized in terms of fit to Z, making possible design of potential memory-modulating peptidic and nonpeptidic substances. Three peptides that neither improved nor impaired retention blocked the amnestic effects of beta-(12-28), a peptide homologous to amyloid beta protein, opening the way to development of substances that can antagonize the neurotoxic effects of amyloid beta protein on neural structures and thus attenuate symptoms and progression of Alzheimer disease.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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