Little is known about the precise mechanism of action of beta-sheet ligands, hampered by the notorious solubility problems involved with protein misfolding and amyloid formation. Recently the nucleation site for the pathogenic aggregation of the Alzheimer's peptide was identified as the KLVFF sequence in the central region of Abeta. A combination of two aminopyrazole ligands with di- or tripepticles taken from this key fragment now furnished water-soluble Abeta-specific ligands which allow model investigations in water. A detailed conformational analysis provides experimental evidence for an increased -sheet content induced in the peptide. Strong indications were also found for the peptide backbone recognition via hydrogen bonds plus hydrophobic contributions between aminopyrazole nuclei and Phe residues. The affinity of these new ligands toward the KKLVFF fragment is highly dependent on their sequence and composition from natural and artificial amino acids. Thus, for the first time, detailed insight is gained into the complexation of beta-sheet ligands with model peptices taken directly from Abeta.