Small oligomers are the major toxic species in many amyloid related diseases, but they are difficult to characterize and target. Here we construct tetra-peptides FXFX (X = F/K), designed to exploit cation-pi, pi-pi and hydrophobic interactions to disrupt the critical F19-L34 contact recently found in A beta(40) oligomers. FRFR accelerates A beta(40) aggregation, and strongly inhibits its binding to lipid membranes, which is important in the context of toxicity. FKFK lacks both of these effects, which correlates with the weaker interaction of K with aromatic residues. Thus it appears possible to tune specific contacts in the oligomer and effectively change its properties. (C) 2017 Published by Elsevier B.V.