| 摘要 |
A cleavage agent is provided to reduce the amount of soluble oligomers of an amyloidogenic peptide or a protein by connecting sites selectively recognizing Soluble assembly of the amyloidogenic peptide or a protein with reactive portions cleaving peptide bonds. A cleavage agent selectively acting on soluble assembly of an amyloidogenic peptide or a protein is represented by the formula(1) of (R)n-(L)m-Z, wherein R is a target recognition site independently selected from the group consisting of A, A-(Y)o-(CH2)p-(Y)o-A, A-(CH=CH)-A, A-(Y)o-(CH2)p-(Y)o-A-(Y)o-(CH2)p-(Y)o-A and A-(Y)o-(CH2)p-(Y)o-A-(Y)o-(CH2)p-(Y)o-A-(Y)o-(CH2)p-(Y)o-A(where A is independently C6-14 aryl, or 5- to 14-membered heteroaryl having at least one hetero atom selected from the group consisting of O, S and N, wherein aryl or heteroaryl is unsubstituted or substituted with at least one substituent independently selected from the group consisting of C1-15 alkyl, hydroxy, C1-15 alkoxy, C1-15 alkylcarbonyloxy, C1-15 alkylsulfonyloxy, amino, mono or di(C1-15)alkylamino, C1-15 alkylcarbonylamino, C1-15 alkylsulfonylamino, C3-15 cycloalkylamino, formyl, C1-15 alkylcarbonyl, carboxy, C1-15 alkyloxycarbonyl, carbamoyl, mono or di(C1-15)alkylcarbamoyl, C1-15 alkylsulfanylcarbonyl, C1-15 alkylsulfanylthiocarbonyl, C1-15 alkoxycarbonyloxy, carbamoyloxy, mono or di(C1-15)alkylcarbamoyloxy, C1-15 alkylsulfanylcarbonyloxy, C1-15 alkoxycarbonylamino, ureido, mono or di or tri(C1-15)alkylureido, C1-15 alkylsulfanylcarbonylamino, mercapto, C1-15 alkylsulfanyl, C1-15 alkyldisulfanyl, sulfo, C1-15 alkoxysulfonyl, sulfamoyl, mono or di(C1-15)alkylsulfamoyl, tri(C1-15)alkylsilanyl and halogen; Y is O or N-Z, wherein Z is hydrogen or C1-9 alkyl; L is a linker; Z is a metal ion-ligand complex as a catalytic site; n is an independent integer from 1 to 6; m and o are independently 0 or 1; p is an integer from 0 to 5). A pharmaceutical composition for preventing or treating amyloidosis such as Alzheimer's disease, type 2 diabetes mellitus, Parkinson's disease, spongiform encepahlopathies or Huntington's disease comprises the cleavage agent of the formula(1) and a pharmaceutically acceptable salt thereof.
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