PEPTIDE OLIGONUCLEOTIDE CONJUGATES

1 . A peptide-oligomer-conjugate of Formula I:

or a pharmaceutically acceptable salt thereof,

wherein:

R 3 is selected from OH, —N(H)CH 2 C(O)NH 2 , —N(C 1-6 -alkyl)CH 2 C(O)NH 2 ,

 R 5 is —C(O)(O-alkyl) x OH, wherein x is 3-10 and each alkyl group is, independently at each occurrence, C 2-6 -alkyl, or R 5 is selected from the group consisting of —C(O)C 1-6 alkyl, trityl, monomethoxytrityl, —(C 1-6 -alkyl)R 6 , —(C 1-6 heteroalkyl)-R 6 , aryl-R 6 , heteroaryl-R 6 , —C(O)O—(C 1-6 alkyl)-R 6 , —C(O)O-aryl-R 6 , —C(O)O-heteroaryl-R 6 , and R 12 ;

R 6 is selected from OH, SH, and NH 2 , or R 6 is O, S, or NH, covalently linked to a solid support;

R 1 is, independently at each occurrence, OH, —NR 7 R 12 , or —NR 7 R 8 ;

each R 7 and R 8 are, independently at each occurrence, H or —C 1-6 alkyl;

R 2 is, independently at each occurrence, selected from the group consisting of H, a nucleobase and a nucleobase functionalized with a chemical protecting-group, wherein the nucleobase, independently at each occurrence, comprises a C 3-6 heterocyclic ring selected from pyridine, pyrimidine, triazinane, purine, and deaza-purine;

z is 8-40;

R 4 is selected from H, —C 1-6 alkyl, —C(O)C 1-6 alkyl, benzoyl, stearoyl, trityl, monomethoxytrityl, dimethoxytrityl, trimethoxytrityl,

and R 12 ;

R 9 is —C(O)(CH 2 ) 6 C(O)— or —C(O)(CH 2 ) 2 S 2 (CH 2 ) 2 C(O)—;

R 10 is —(CH 2 ) 2 OC(O)N((CH 2 ) 6 N(H)C(═NH)NH 2 ) 2 ;

R 11 is selected from OH and —NR 7 R 8 ;

R 12 is selected from the group consisting of:

n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

p is 2, 3, 4, or 5;

R 13 is a bond, or R 13 is selected from the group consisting of:

 R 15 and R 19 are, independently at each occurrence, selected from the group consisting of H, —C 14 alkyl, —CH(—C 14 alkyl) 2 , and —(CH 2 ) 3 NH—C(═NH)—NH 2 ;

 t and w are, independently at each occurrence, 2, 3, 4, or 5;

 R 14 is selected from the group consisting of:

 R 17 is H or —C 1-4 alkyl;

 R 20 is selected from the group consisting of H, —C 1-4 alkyl, —CH(—C 1-4 alkyl) 2 , and —(CH 2 ) 3 NH —C(═NH)—NH 2 ;

 v and q are, independently at each occurrence, 2, 3, 4, or 5;

 R 16 is selected from the group consisting of:

  R 21 and R 22 are, independently at each occurrence, H or —C 1-4 alkyl;

  R 18 is selected from the group consisting of H, —C(O)C 1-6 alkyl, benzoyl, and stearoyl;

  r is 1, 2, 3, 4, 5, 6, 7, 8, or 9; and

  y and u are, independently at each occurrence, 2, 3, 4, or 5;

provided that only one of the following conditions is present: 1) R 1 is NR 7 R 12 ; 2) R 4 is R 12 ; or 3) R 3 is

2 - 9 . (canceled)

10 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the peptide-oligomer-conjugate of Formula I is a peptide-oligomer-conjugate of Formula Ia:

wherein R 5 is —C(O)(O-alkyl) x OH, wherein x is 3-10 and each alkyl group is, independently at each occurrence, C 2-6 -alkyl, or R 5 is selected from the group consisting of —C(O)C 1-6 alkyl, trityl, and monomethoxytrityl.

11 - 12 . (canceled)

13 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the peptide-oligomer-conjugate of Formula I is a peptide-oligomer-conjugate of Formula Ib:

wherein R 4 is selected from H, —C 1-6 alkyl, —C(O)C 1-6 alkyl, benzoyl, stearoyl, trityl, monomethoxytrityl, dimethoxytrityl, and trimethoxytrityl.

14 - 15 . (canceled)

16 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 16 is selected from the group consisting of:

17 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 16 is

18 . (canceled)

19 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 12 is

20 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein r is 3, 4, 5, 6, 7, or 8.

21 - 23 . (canceled)

24 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein z is 8-25.

25 - 28 . (canceled)

29 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

each R 2 is a nucleobase, wherein the nucleobase, independently at each occurrence, comprises a C 4-6 -heterocyclic ring selected from pyridine, pyrimidine, triazinane, purine, and deaza-purine.

30 - 31 . (canceled)

32 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

each R 2 is a nucleobase, wherein the nucleobase, independently at each occurrence, is selected from the group consisting of adenine, guanine, cytosine, 5-methyl-cytosine, thymine, uracil, and hypoxanthine.

33 - 44 . (canceled)

45 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 2, 3, 4, 5, 6, or 7.

46 - 55 . (canceled)

56 . The peptide-oligomer-conjugate of claim 1 , wherein the peptide-oligomer-conjugate of Formula I is a peptide-oligomer-conjugate of Formula Ic:

or a pharmaceutically acceptable salt thereof,

wherein:

R 3 is OH,

 R 5 is —C(O)(O-alkyl) x OH, wherein x is 3-10 and each alkyl group is, independently at each occurrence, C 2-6 -alkyl, or R 5 is —C(O)C 1-6 alkyl;

R 1 is, independently at each occurrence, OH or —NR 7 R 8 ;

each R 7 and R 8 are independently at each occurrence —C 1-6 alkyl;

R 2 is, independently at each occurrence, selected from the group consisting of H, adenine, 2,6-diaminopurine, 7-deaza-adenine, guanine, 7-deaza-guanine, hypoxanthine, cytosine, 5-methyl-cytosine, thymine, and uracil;

z is 8-40;

R 12 is selected from the group consisting of:

 n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

 p is 2, 3, 4, or 5;

 R 13 is a bond;

 R 14 is selected from the group consisting of:

  R 17 is H or —C 1-4 alkyl;

  R 16 is selected from the group consisting of:

  R 21 is H or —C 1-4 alkyl;

  R 18 is of H or —C(O)C 1-6 alkyl; and

  r is 1, 2, 3, 4, 5, 6, 7, 8, or 9.

57 - 60 . (canceled)

61 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 16 is

62 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein r is 5, 6, or 7.

63 . The peptide-oligomer-conjugate of claim 56 , or a pharmaceutically acceptable salt thereof, wherein the peptide-oligomer-conjugate is selected from the group consisting of:

wherein

R 18 is selected from H and —C(O)CH 3 .

64 - 65 . (canceled)

66 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the oligonucleotide comprises a targeting sequence having sequence complementarity to an RNA target.

67 . The peptide-oligomer-conjugate of claim 66 , or a pharmaceutically acceptable salt thereof, wherein the RNA target is a cellular RNA target.

68 . The peptide-oligomer-conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the targeting sequence has sufficient sequence complementarity to bind to the RNA target.

69 . (canceled)

70 . A method of treating a central nervous system disorder, a muscle disease, a viral infection, or a bacterial infection in a subject in need thereof, comprising administering to the subject a peptide-oligomer-conjugate of claim 1 .

71 . The method of claim 70 , wherein the muscle disease, central nervous system disorder, viral infection, or bacterial infection is selected from one or more of: Duchenne Muscular Dystrophy, marburg virus infection, ebola virus infection, influenza virus infection, dengue virus infection, Mycobacterium tuberculosis infection, and spinal muscular atrophy.

72 - 74 . (canceled)