| 主权项 |
1. A pharmaceutical composition characterized by comprising an active ingredient wherein the active ingredient is a polyamide compound, or a pharmaceutically acceptable salt thereof, binding to a target double-stranded DNA, wherein said target double-stranded DNA comprises at least one nucleotide pair selected from the group consisting of an A/T pair consisting of the first A of the following sense-stranded DNA and the corresponding T, an A/T pair consisting of the 8th A of the following sense-stranded DNA and the corresponding T, a G/C pair consisting of the 9th G of the following sense-stranded DNA and the corresponding C, a G/C pair consisting of the 14th G of the following sense-stranded DNA and the corresponding C, a T/A pair consisting of the 15th T of the following sense-stranded DNA and the corresponding A, an A/T pair consisting of the 16th A of the following sense-stranded DNA and the corresponding T, an A/T pair consisting of the 17th A of the following sense-stranded DNA and the corresponding T, a C/G pair consisting of the 19th C of the following sense-stranded DNA and the corresponding G, a G/C pair consisting of the 20th G of the following sense-stranded DNA and the corresponding C, a C/G pair consisting of the 21st C of the following sense-stranded DNA and the corresponding G, a T/A pair consisting of the 23rd T of the following sense-stranded DNA and the corresponding A, an A/T pair consisting of the 25th A of the following sense-stranded DNA and the corresponding T, in the double stranded DNA of the following formula (1):[Chem. 1]5′-ATGGCAGAGCCCGGTAATCGCATAA-3′3′-TACCGTCTCGGGCCATTAGCGTATT-5′(1) which consists of the sense-stranded DNA having a base sequence of 5′-ATGGCAGAGCCCGGTAATCGCATAA-3′ (SEQ ID NO: 1) and the antisense-stranded DNA having a base sequence of 5′-TTATGCGATTACCGGGCTCTGCCAT-3′ (SEQ ID NO: 2); and at least one end of said target double-stranded DNA is an A/T or T/A pair;
(1) a residue of the polyamide compound, corresponding to the A/T pair or T/A pair at one end thereof is a turn structure selected from the group consisting of γ-aminobutyric acid residue, (R)2,4-diaminobutyric acid residue, and 5-aminovaleric acid residue, wherein the hydrogen atom of the residues may be substituted with an alkyl group having 1 to 4 carbon atoms, an amino group, a hydroxyl group, a carboxyl group, or —NH3;(2) the binding region of the polyamide compound, corresponding to the target double-stranded DNA except for the A/T pair or T/A pair at one end thereof, is composed of
(a) Im/Py, or Im/β, corresponding to the G/C pair of the target double-stranded DNA,(b) Py/Im, or β/Im, corresponding to the C/G pair of the target double-stranded DNA,(c) Py/Py, Py/Hp, Py/β, β/Py, or β/β corresponding to the A/T pair of the target double-stranded DNA, and(d) Py/Py, Hp/Py, Py/β, β/Py, or β/β, corresponding to the T/A pair of the target double-stranded DNA, (wherein Im is N-methylimidazole, Py is N-methylpyrrole, Hp is 3-hydroxy-N-methylpyrrole, and β is β-alanine; and Im/β corresponding to the G/C pair and β/Im corresponding to the C/G pair can be only used in the case of a successive Im•/Im•β corresponding to a successive G•C/G•C pair or a successive β•Im/β•Im corresponding to a successive C•G/C•G pair; and the hydrogen atom of the Im residue, Py residue, Hp residue, or β residue may be substituted to an alkyl group having 1 to 4 carbon atoms, an amino group, a hydroxyl group, a carboxyl group, or —NH3), and the binding region comprises at least one residue pair of Im/β corresponding to the G/C pair, β/Im corresponding to the C/G pair, β/corresponding to the A/T pair, or β/β corresponding to the T/A pair, of the target double stranded DNA;
(3) an end of the polyamide compound corresponding to the 5′end of the other end of the target double-stranded DNA is an amino group of Im residue, an amino group of Py residue, an amino group of Hp residue, an amino group of β-alanine, a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, a carboxyl group, or an acyl group having 1 to 4 carbon atoms; an end of the polyamide compound corresponding to the 3′end of the other end of the target double-stranded DNA is a carboxyl group of Im residue, a carboxyl group of Py residue, a carboxyl group of Hp residue, a carboxyl group of β-alanine, an N,N-dimethylaminopropyl residue, or a β-alanine N,N-dimethylaminopropyl residue. |
