TERTIARY AMINO LIPIDATED CATIONIC PEPTIDES FOR NUCLEIC ACID DELIVERY

1 . A tertiary amino lipidated and/or PEGylated cationic peptide compound of formula (I) or a salt thereof:

wherein:

m is an integer from 0 to 10;

n is an integer from 0 to 5;

s is an integer from 0 to 5;

t is an integer from 0 to 10;

wherein at least one of m, n, s, and t is nonzero;

r is an integer from 1 to 20;

each o is independently an integer 0, 1, or 2;

each q is independently an integer 0, 1, or 2;

each p is independently an integer 1 or 2;

R 1 is —H, alkyl, alkylaryl, —COR 1a or a lipid moiety,

wherein Ria is —H, —OH, alkyl, aryl, alkylaryl, —O-alkyl, or —O-alkylaryl;

each R 2 is independently an ethylene glycol moiety of the formula —CH 2 CH 2 O(CH 2 CH 2 O) u CH 3 , and wherein each u is independently an integer from 2 to 200;

each R 3 is independently a lipid moiety;

each R 4 is independently a neutral spacer moiety or a lipid moiety;

each R 5 is independently a cationic moiety;

each R 6 is independently an ethylene glycol moiety of the formula —CH 2 CH 2 O(CH 2 CH 2 O) v CH 3 , and wherein each v is independently an integer from 2 to 200;

R 7 is —H, alkyl, acyl, —OH, —OR 7a , —NH 2 , —NHR 7a , or a lipid moiety, wherein R 7a is alkyl, acyl, or a lipid moiety; and

each R a and R b is independently —H, C 1 -C 4 -alkyl, or a side chain moiety found on a naturally- or non-naturally-occurring amino acid.

2 .- 36 . (canceled)

37 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 1 , wherein m is 0; n is 0; s is an integer from 1 to 5; t is 0; r is an integer from 1 to 5; o is 0; q is 2; and p is 1, and having a structure:

38 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 37 , wherein:

R 1 is H;

each R 3 independently is C 8 -C 24 alkyl;

each R 4 is independently a neutral spacer moiety that is a C 1 -C 4 -alkyl substituted by cycloalkyl, heterocyclylalkyl, alkylaryl, arylalkyl, alkylheteroaryl, heteroarylalkyl, alkoxy, alkoxyalkyl, or hydroxyalkyl, wherein each cycloalkyl, heterocyclylalkyl, alkylaryl, arylalkyl, alkylheteroaryl, heteroarylalkyl, alkoxy, alkoxyalkyl, or hydroxyalkyl is optionally substituted with one or more substituents —OH, halo, or alkoxy;

each R 5 is independently selected from the group consisting of aminoalkyl, alkylaminoalkyl, aminoalkylaminoakyl, guanidinoalkyl, N-heterocyclylalkyl, and N-heteroaryl;

R 7 is NH 2 ; and

each of R a and R b is H.

39 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 37 , wherein

each R 4 independently is selected from the group consisting of

and

each R 5 is independently selected from the group consisting of

40 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 1 , wherein m is 0; n is 0; s is an integer from 1 to 5; t is 0; r is an integer from 2 to 10; o is 0; q is 0; and p is 1, and having a structure:

41 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 40 , wherein

R 1 is H;

each R 3 independently is C 8 -C 24 alkyl;

each R 5 is independently selected from the group consisting of aminoalkyl, alkylaminoalkyl, aminoalkylaminoakyl, guanidinoalkyl, N-heterocyclylalkyl, and N-heteroaryl;

R 7 is NH 2 ; and

each of R a and R b is H.

42 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 40 , wherein

each R 3 independently is

and

each R 5 is independently selected from the group consisting of

43 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 1 , wherein m is 0; n is 0; s is 3 or 4; t is 0; r is 1; o is 0; q is 2; and p is 2, and having a structure:

44 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 43 , wherein:

R 1 is H or alkyl;

each R 3 independently is C 8 -C 24 alkyl;

each R 4 is independently a neutral spacer moiety that is a C 1 -C 4 -alkyl substituted by cycloalkyl, heterocyclylalkyl, alkylaryl, arylalkyl, alkylheteroaryl, heteroarylalkyl, alkoxy, alkoxyalkyl, or hydroxyalkyl, wherein each cycloalkyl, heterocyclylalkyl, alkylaryl, arylalkyl, alkylheteroaryl, heteroarylalkyl, alkoxy, alkoxyalkyl, or hydroxyalkyl is optionally substituted with one or more substituents —OH, halo, or alkoxy;

each R 5 is independently selected from the group consisting of aminoalkyl, alkylaminoalkyl, aminoalkylaminoakyl, guanidinoalkyl, N-heterocyclylalkyl, N-heteroaryl, hydroxyalkyl, hydroxyether, alkoxyalkyl, and hydroxylheteroalkyl;

R 7 is NH 2 ; and

each of R a and R b is H.

45 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 43 , wherein:

each R 3 independently is

each R 4 independently is selected from the group consisting of

and

each R 5 is independently selected from the group consisting of

46 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 1 , wherein m is 0; n is 0; s is 3 or 4; t is 0; r is 3; o is 0; q is 2; and p is 1, and having a structure:

47 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 46 , wherein:

R 1 is H or alkyl;

each R 3 independently is C 8 -C 24 alkyl;

each R 4 is independently a neutral spacer moiety that is a C 1 -C 4 -alkyl substituted by cycloalkyl, heterocyclylalkyl, alkylaryl, arylalkyl, alkylheteroaryl, heteroarylalkyl, alkoxy, alkoxyalkyl, or hydroxyalkyl, wherein each cycloalkyl, heterocyclylalkyl, alkylaryl, arylalkyl, alkylheteroaryl, heteroarylalkyl, alkoxy, alkoxyalkyl, or hydroxyalkyl is optionally substituted with one or more substituents —OH, halo, or alkoxy;

each R 5 is independently selected from the group consisting of aminoalkyl, alkylaminoalkyl, aminoalkylaminoakyl, guanidinoalkyl, N-heterocyclylalkyl, and N-heteroaryl, hydroxyalkyl, hydroxyether, alkoxyalkyl, and hydroxylheteroalkyl;

R 7 is NH 2 ; and

each of R a and R b is H.

48 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 46 , wherein:

each R 3 independently is

each R 4 independently is selected from the group consisting of

and

each R 5 is independently selected from the group consisting of

49 . A tertiary amino lipidated and PEGylated peptide compound of formula (I) or salt thereof:

wherein:

m is an integer from 0 to 10;

n is an integer from 0 to 5;

s is an integer from 0 to 10;

t is an integer from 0 to 5;

wherein at least one of m and t is nonzero, and wherein at least one of n and s is nonzero;

r is an integer from 1 to 20;

each o is independently an integer 0, 1, or 2;

each q is independently an integer 0, 1, or 2;

each p is independently an integer 1 or 2;

R 1 is —H, alkyl, alkylaryl, —COR 1a or a lipid moiety,

wherein R 1a is —H, —OH, alkyl, aryl, alkylaryl, —O-alkyl, or —O-alkylaryl;

each R 2 is independently an ethylene glycol moiety of the formula —CH 2 CH 2 O(CH 2 CH 2 O) u CH 3 , and wherein each u is independently an integer from 2 to 200;

each R 3 is independently a lipid moiety;

each R 4 is independently a neutral spacer moiety or a lipid moiety;

each R 5 is independently a cationic moiety;

each R 6 is independently an ethylene glycol moiety of the formula

CH 2 CH 2 O(CH 2 CH 2 O) v CH 3 , and wherein each v is independently an integer from 2 to 200;

R 7 is —H, alkyl, acyl, —OH, —OR 7a , —NH 2 , —NHR 7a , or a lipid moiety, wherein R 7a is alkyl, acyl, or a lipid moiety; and

each R a and R b is independently —H, C 1 -C 4 -alkyl, or a side chain moiety found on a naturally- or non-naturally-occurring amino acid.

50 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 49 , wherein m is 1; n is 0; s is 3 or 4; t is 0; r is 1 or 2; o is 0; q is 2; and p is 1, and having a structure:

51 . The tertiary amino lipidated and/or PEGylated cationic peptide compound of claim 50 , wherein:

R 1 is H;

R 2 is an ethylene glycol moiety of the formula —CH 2 CH 2 O(CH 2 CH 2 O) u CH 3 , and wherein each u is independently an integer from 2 to 50;

each R 3 independently is C 8 -C 24 alkyl;

each R 4 is independently a neutral spacer moiety that is a C 1 -C 4 -alkyl substituted by cycloalkyl, heterocyclylalkyl, alkylaryl, arylalkyl, alkylheteroaryl, heteroarylalkyl, alkoxy, alkoxyalkyl, or hydroxyalkyl, wherein each cycloalkyl, heterocyclylalkyl, alkylaryl, arylalkyl, alkylheteroaryl, heteroarylalkyl, alkoxy, alkoxyalkyl, or hydroxyalkyl is optionally substituted with one or more substituents —OH, halo, or alkoxy;

each R 5 is independently selected from the group consisting of aminoalkyl, alkylaminoalkyl, aminoalkylaminoakyl, guanidinoalkyl, N-heterocyclylalkyl, and N-heteroaryl, hydroxyalkyl, hydroxyether, alkoxyalkyl, and hydroxylheteroalkyl;

R 7 is NH 2 ; and

each of R a and R b is H.

52 . A complex comprising one or more of the tertiary amino lipidated and/or PEGylated cationic peptide compounds of claim 1 , complexed to a polyanionic compound.

53 . The complex of claim 52 , wherein the polyanionic compound comprises a nucleic acid.

54 . The complex of claim 52 , wherein the polyanionic compound comprises a nucleic acid and wherein the nucleic acid is an mRNA encoding a polypeptide.

55 . The complex of claim 52 , wherein the polyanionic compound comprises a nucleic acid and wherein the complex comprises at least one of the tertiary amino lipidated and/or PEGylated cationic peptide and the nucleic acid at a mass ratio of between 0.5:1 and 50:1.

56 . The complex of claim 52 , wherein the complex comprises: the one or more tertiary amino lipidated and/or PEGylated cationic peptide compounds, a nucleic acid, a phospholipid, a structural lipid, and a PEG lipid.

57 . A method of delivering a polyanionic compound to a cell comprising contacting the cell with the complex of claim 52 .

58 . The method of claim 57 , wherein the polyanionic compound comprises a nucleic acid which is the mRNA encoding a polypeptide and the cell expresses the polypeptide after being contacted with the complex.

59 . A method of forming the complex of claim 52 , comprising contacting the tertiary amino lipidated and/or PEGylated cationic peptide compound with the polyanionic compound.

60 . A compound selected from the compounds listed in Table 1A.