Karolinska Innovations Ab

Neurochem (International) Limited

Johan Thyberg

Christer Nordstedt

Lars Terenius

Lars O Tjernberg

Jan Näslund

Jan N&auml;slund

The invention relates to compounds of formula (I) or (II), which are of interest especially for inhibition of polymerization of amyloid &#x3b2; peptide, as model substances for synthesis of amyloid &#x3b2; 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&#x2032;-Leu-X&#x2032;-Z&#x2032;-B&#x2032;-Rin which X&#x2032; means any group or amino acid imparting to the compound according to formula (I) the ability to bind to the KLVFF-sequence in amyloid &#x3b2; peptide, or two amino acids imparting the same ability, but with the proviso that one is not proline; Y&#x2032; means any amino acid; Z&#x2032; means any non-acidic amino acid; A&#x2032; means a direct bond or an &#x3b1;-amino acid bonded at the carboxyl terminal of the &#x3b1;-carboxy group or a di-, tri-, tetra- or pentapeptide bonded at the carboxyl terminal of the &#x3b1;-carboxy group; B&#x2032; means a direct bond or an &#x3b1;-amino acid bonded at the &#x3b1;-nitrogen or a di-, tri, tetra- or pentapeptide bonded at the &#x3b1;-nitrogen of the N-terminal &#x3b1;-amino acid; Ris H or &#x2014;CO&#x2014;Rbonded at the &#x3b1;-amino group of A&#x2032;; Ris H, &#x2014;ORor NRR, all bonded to the &#x3b1;-carboxyl group of the &#x3b1;-carboxyterminal of B&#x2032;; 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 &#x2014;(CH)&#x2014; where n is 4-5; and Rand Rtogether can form a hydrocarbon ring or heterocyclic ring; all &#x3b1;-amino acids being either D- or L-isomers.

Peptide binding the KLVFF-sequence of amyloid-&#x3b2;

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,&mdash;A&prime;&mdash;Y&prime;&mdash;Leu&mdash;X&prime;&mdash;Z&prime;&mdash;B&prime;&mdash;R,in which X&prime; 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&prime; means any amino acid; Z&prime; means any non-acidic amino acid; A&prime; 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&prime; 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 &mdash;CO&mdash;R,bonded at the &agr;-amino group of A&prime;; R,is H, &mdash;OR,or NR,R,, all bonded to the &agr;-carboxyl group of the &agr;-carboxyterminal of B&prime;; 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 &mdash;(CH,),&mdash; 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.

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

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Stockholm, Sweden

Johan Thyberg