Peptide binding the klvff-sequence of amyloid-β

Abstract

The invention relates to compounds of formula (I) or (II), which are of interest especially for inhibition of polymerization of amyloid β peptide, as model substances for synthesis of amyloid β 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′-Rin 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 β 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 α-amino acid bonded at the carboxyl terminal of the α-carboxy group or a di-, tri-, tetra- or pentapeptide bonded at the carboxyl terminal of the α-carboxy group; B′ means a direct bond or an α-amino acid bonded at the α-nitrogen or a di-, tri, tetra- or pentapeptide bonded at the α-nitrogen of the N-terminal α-amino acid; Ris H or —CO—Rbonded at the α-amino group of A′; Ris H, —ORor NRR, all bonded to the α-carboxyl group of the α-carboxyterminal of B′; Rand Rare straight or branched carbon chain of 1-4 carbon atoms; Rand Rare independently H, alkyl, cycloalyl, aryl or substituted aryl or together are —(CH)— where n is 4-5; and Rand Rtogether can form a hydrocarbon ring or heterocyclic ring; all α-amino acids being either D- or L-isomers.