Antisense antibacterial compounds and methods

An antisense morpholino oligomer of formula (I):

• or a pharmaceutically acceptable salt thereof,
• where each Nu is a nucleobase which taken together forms a targeting sequence, where the targeting sequence is selected from:
• a)
• SEQ ID NO:
• 2
• (TGCTCATACTC);
• bc)
• SEQ ID NO:
• 3
• (CGTTTC ATT A);
• c)
• SEQ ID NO:
• 4
• (TTT ATC CAT TG);
• d)
• SEQ ID NO:
• 6
• (GTC TAT TCT CC);
• e)
• SEQ ID NO:
• 7
• (GAC ATG TCT AT);
• f)
• SEQ ID NO:
• 8
• (TGG TTC TGC AT);
• g)
• SEQ ID NO:
• 9
• (AGT TTC TCT CC);
• h)
• SEQ ID NO:
• 10
• (GTT CAA ACA TA);
• i)
• SEQ ID NO:
• 11
• (CGC TCA TCT AA);
• j)
• SEQ ID NO:
• 12
• (TTC CTG CCA TA);
• k)
• SEQ ID NO:
• 13
• (TTT GAT CAT CG);
• l)
• SEQ ID NO:
• 14
• (AGT GCT CTA CC);
• m)
• SEQ ID NO:
• 15
• (GCC TGT TAT CC);
• n)
• SEQ ID NO:
• 17
• (TTG CGC TCG TT);
• o)
• SEQ ID NO:
• 18
• (GGC TGC TGG CA);
• and
• p)
• SEQ ID NO:
• 19
• (TCA TCT TTG CT);
• and where thymine bases (T) may be uracil bases (U)
• X is 9 to 38;
• T is selected from OH and a moiety of the formula:
• where each R4 is independently C1-C6 alkyl, and R5 is selected from an electron pair and H, and R6 is selected from OH, —N(R7)CH2C(O)NH2, and a moiety of the formula:
• where:
• R7 is selected from H and C1-C6 alkyl, and
• R8 is selected from G, —C(O)—R9OH, acyl, trityl, and 4-rnethoxytrityl, where:
• R9 is of the formula —(O-alkyl)y- where y is an integer from 3 to 10 and each of the y alkyl groups is independently selected from C2-C6 alkyl;
• each instance of R1 is —N(10)2R11 where each R10 is independently C2-C6 alkyl, and R11 is selected from an electron pair and H;
• R2 is selected from H, G, acyl, trityl, 4-methoxytrityl, benzoyl, stearoyl, and a moiety of the formula:
• where L is selected from —C(O)(CH2)6C(O)— and —C(O)(CH2)2S2(CH2)2C(O)— and each R12 is of the formula —(CH2)2OC(O)N(R14)2 where each R14 is of the formula —(CH2)6NHC(═NH)NH2;
• and
• R3 is selected from an electron pair, H, and C1-C6 alkyl,
• where G is a cell penetrating peptide (“CPP”) and linker moiety selected from —C(O)(CH2)5NH—CPP, —C(O)(CH2)2NH—CPP, —C(O)(CH2)2N HC(O)(CH2)5NH—CPP, and —C(O)CH2NH—CPP, or G is of the formula:
• where the CPP is attached to the linker moiety by an amide bond at the CPP carboxy terminus, with the proviso that only one instance of G is present,
• where the targeting sequence specifically hybridizes to a bacterial nRNA target sequence that encodes a protein associated with a biochemical pathway and/or cellular process, or a ribosomal RNA (rRNA) target sequence.