Molecular tweezers for the treatment of amyloid-related diseases

摘要

This invention provides novel compositions to inhibit the aggregation of amyloid proteins. In various embodiments the compositions comprise a molecular tweezers that binds lysine and/or arginine and thereby inhibits the aggregation of amyloidogenic proteins.;

主权项

1. A molecular tweezers, said molecular tweezers having one of the formulas I-IV:or a salt thereof, where:
C1, C2, C3, and C4 are independently selected from the group consisting of H, Cl, Br, I, OR, NR2, NO2, CO2H, and CO2R, where R is alkyl, aryl, or H; or C1 and C2 and/or C3 and C4 form an aliphatic or aromatic ring; A is selected from the group consisting of phosphate, hydrogen phosphate, alkylphosphamide, arylphosphamide, sulfate, and alkylcarboxylate; B is selected from the group consisting of phosphate, hydrogen phosphate, alkylphosphonate, arylphosphonate, alkylphosphamide, arylphosphamide, and sulfate, or B has the formula:
—X—S—Y—Zwhere:
X is present or absent and when present is —(C═O)—; S is a spacer; Y is selected from the group consisting of an ester, an amide, a urethane, and a sulfonic ester link; and Z is selected from the group consisting of a detectable label, a protein, a nucleic acid, a sugar, and a glycoprotein; and said molecular tweezers does not have the formula of TW2.