Non-peptidic cell-penetrating motifs

1. A compound having a structure according to Formula III:

wherein:

A is a non-peptidic multivalent moiety, wherein A is selected from the group consisting of:

(a) a carbocyclyl;

(b) a heterocyclyl;

(c) an amino acid;

(d) an aryl;

(e) a heteroaryl;

(f) nitrogen;

(g) a non-peptidic moiety comprising aspartic acid, glutamic acid, or lysine, or combinations thereof;

(h) a carbohydrate;

(i) a sugar alcohol; and

(j) a polymeric alcohol;

each X is independently a first bonding group that links R 1 to A, wherein X is a divalent group;

each Y is a second bonding group that links A to a guanidine or guanidinium group; wherein

guanidine or guanidinium group refers to the structure

each Z is independently a lone pair, H, halogen, CN, NO 2 , NH 2 , or alkyl;

each R 1 is independently a hydrophobic amino acid residue, or analog thereof, having an aromatic side chain;

each R 2 is independently absent or a moiety comprising hydrophobic residue;

each R 3 is independently a cargo moiety;

each m is independently an integer from 0 to 10;

each n is independently an integer from 0 to 6;

each p is 1 to 3;

q is 2 to 7; and

s is an integer from 1 to 3.

2. The compound of claim 1 , wherein A is an aryl or heteroaryl.

3. The compound of claim 1 , wherein A is nitrogen.

4. The compound of claim 1 , wherein X comprises a bonding group selected from

wherein each a is independently number from 0 to 10.

5. The compound of claim 1 , wherein Y is selected from N, S,

wherein each b is independently a number from 0 to 10.

6. The compound of claim 1 , wherein R 2 is independently selected from the group consisting of:

(a) a moiety comprising an aryl or heteroaryl moiety and

(b) an amino acid residue or analog thereof, having an aromatic side chain.

7. The compound of claim 1 , wherein R 1 and R2, if present, is independently an amino acid selected from the group consisting of phenylalanine, tryptophan, naphthylalanine, phenylglycine, homophenylalanine, tyrosine, cyclohexylglycine, piperidine-2-carboxylic acid, cyclohexylalanine, 3-(3-benzothienyl)-alanine, 3-(2-quinolyl)-alanine, O-benzylserine, 3-(4-(benzyloxy)phenyl)-alanine, S-(4-methylbenzyl)cysteine, N-(naphthalen-2-yl)glutamine, and 3-(1,1′-biphenyl-4-yl)-alanine, each of which is optionally substituted with one or more substituents.

8. The compound of claim 1 , wherein n is 1, 2, or 3; wherein m is 3, 4, 5, 6, or 7; and wherein p is 2 or 3.

9. The compound of claim 1 , wherein Y is N and p is 2.

10. The compound of claim 1 , wherein q is 2 or 3.

11. The compound of claim 1 , wherein s is 1.

12. A compound having a structure according to Formula IV:

wherein:

A is a non-peptidic multivalent moiety;

each X is independently a first bonding group that links R 1 to A, wherein X is a divalent group;

each Z is independently a lone pair, H, halogen, CN, NO 2 , NH 2 , or alkyl;

each R 1 is independently a hydrophobic amino acid residue, or analog thereof, having an aromatic side chain;

each R 2 is independently absent or a moiety comprising hydrophobic residue;

each R 3 is independently a cargo moiety;

each m is independently an integer from 0 to 10; and

each n is independently an integer from 0 to 6.

13. The compound of claim 12 , wherein A is an aryl, heteroaryl, or nitrogen.

14. A compound having the structure of:

wherein:

each Z is independently a lone pair, H, halogen, CN, NO 2 , NH 2 , or alkyl;

each R 2 is independently absent or a moiety comprising hydrophobic residue; and

each R 3 is independently a cargo moiety.

15. The compound of claim 1 , wherein the cargo moiety comprises a therapeutic agent.

16. A pharmaceutical composition comprising a compound of claim 1 .

17. The compound of claim 1 , wherein R 1 is a D-amino acid residue.