Peptide binding the klvff-sequence of amyloid-&bgr;

Abstract

The invention relates to compounds of formula (I) or (II), which are of interest especially for inhibition of polymerization of amyloid &bgr; peptide, as model substances for synthesis of amyloid &bgr; peptide-ligands, as tools for the identification of other organic compounds with similar functional properties and/or as ligands for detection of amyloid deposits using e.g., positron emission tomography (PET). Formula (II) is: R,—A′—Y′—Leu—X′—Z′—B′—R,in which X′ means any group or amino acid imparting to the compound according to formula (I) the ability to bind to the KLVFF-sequence in amyloid &bgr; peptide, or two amino acids imparting the same ability, but with the proviso that one is not proline; Y′ means any amino acid; Z′ means any non-acidic amino acid; A′ means a direct bond or an &agr;-amino acid bonded at the carboxyl terminal of the &agr;-carboxy group or a di-, tri-, tetra- or pentapeptide bonded at the carboxyl terminal of the &agr;-carboxy group; B′ means a direct bond or an &agr;-amino acid bonded at the &agr;-nitrogen or a di-, tri-, tetra- or pentapeptide bonded at the &agr;-nitrogen of the N-terminal &agr;-amino acid; R,is H or —CO—R,bonded at the &agr;-amino group of A′; R,is H, —OR,or NR,R,, all bonded to the &agr;-carboxyl group of the &agr;-carboxyterminal of B′; R,and R,are straight or branched carbon chain of 1-4 carbon atoms; R,and R,are independently H, alkyl, cycloalkyl, aryl or substituted aryl or together are —(CH,),— where n is 4-5; and R,and R,together can form a hydrocarbon ring of heterocyclic ring; all &agr;-amino acids being either D- or L-isomers.