TOPOGRAPHY OF A BINDING-SITE FOR SMALL AMNESTIC PEPTIDES DEDUCED FROMSTRUCTURE-ACTIVITY STUDIES - RELATION TO AMNESTIC EFFECT OF AMYLOID BETA-PROTEIN

Four peptides homologous to amyloid beta protein containing the Val-Ph e-Phe (VFF) sequence administered intracerebroventricularly after trai ning caused amnesia for footshock active avoidance training in mice. R esults with VFF and other peptides containing VFF or portions thereof were used to generate a topographic map for a hypothetical binding sur face for amnestic peptides, termed Z. Effects on retention of footshoc k active avoidance training were rationalized in terms of fit to Z, ma king possible design of potential memory-modulating peptidic and nonpe ptidic substances. Three peptides that neither improved nor impaired r etention blocked the amnestic effects of beta-(12-28), a peptide homol ogous to amyloid beta protein, opening the way to development of subst ances that can antagonize the neurotoxic effects of amyloid beta prote in on neural structures and thus attenuate symptoms and progression of Alzheimer disease.