| CPC C07K 14/003 (2013.01) [A61K 8/64 (2013.01); A61Q 19/08 (2013.01); A61K 38/00 (2013.01)] | 5 Claims |
|
1. A peptide nucleic acid derivative represented by Formula I, or a pharmaceutically acceptable salt thereof, for inducing exon skipping within human ACC2 pre-mRNA:
 wherein,
n is an integer between 11 and 15;
the compound of Formula I possesses at least a 10-mer complementary overlap with the 18-mer pre-mRNA sequence of [(5′-3′) GGCCAUUUCGUCAGUAUC] (SEQ ID NO: 7) in the human ACC2 pre-mRNA;
the compound of Formula I is fully complementary to the human ACC2 pre-mRNA, or partially complementary to the human ACC2 pre-mRNA with one or two mismatches;
S1, S2, . . . , Sn-1, Sn, T1, T2, . . . , Tn-1, and Tn are hydrido radical;
X and Y independently represent hydrido, or substituted or non-substituted alkyloxycarbonyl radical;
Z represents substituted or non-substituted amino radical; and
B1, B2, . . . , Bn-1, and Bn are independently selected from natural nucleobases including adenine, thymine, guanine, cytosine and uracil, and unnatural nucleobases; and,
at least four of B1, B2, . . . , Bn-1, and Bn are independently selected from unnatural nucleobases represented by Formula II, Formula III, or Formula IV
 wherein,
R1, R2, R3, R4, R5 and R6 are hydrido radical;
L1 represents —(CH2)2—O—(CH2)2—, —CH2—O—(CH2)2—, —CH2—O—(CH2)3—, —CH2—O—(CH2)4—, or —CH2—O—(CH2)5—; and,
L2 and L3 are independently selected from —(CH2)2—O—(CH2)2—, —(CH2)3—O—(CH2)2—, —(CH2)2—O—(CH2)3—, —(CH2)2—, —(CH2)3—, —(CH2)4—, —(CH2)5—, —(CH2)6—, —(CH2)r, and —(CH2)8—.
|