Peptide derivatives 1-5, incorporating synthetic non-proteinogenic amino acids, related to the beta-amyloid 17-21 fragment of the amyloidogenic Abeta(1-40), and the N-protected decapeptide 6, corresponding to a dimeric sequence of the same fragment, have been synthesized. These compounds were designed by using Soto's pentapeptide Ac-LPFFD-NH(2) (iAbeta5p) as lead compound. Their activity as inhibitors of fibrillogenesis and stability against enzymatic degradation have been determined. Compounds 1, 5 and 6 are potent inhibitors in comparison to the lead compound. Exposure to chymotrypsin of peptide derivatives 1-5, all containing unnatural amino acids, shows increased stability as compared with iAbeta5p and 6. Conformational properties of the new compounds have been determined by CD and FT-IR spectroscopies.