Karolinska Innovations Ab

Neurochem (International) Limited

Amyloidia Sweden Ab

Lars Terenius

Johan Thyberg

Lars O Tjernberg

Christer Nordstedt

Jan Näslund

Jan N&auml;slund

Jüri Jarvet

Vladana Vukojevic

Rudolf Rigler

Sebastian Wärmländer

Ann Tiiman

Astrid Gräslund

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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Uppsala, Sweden

Lars Terenius