Compositions and methods for reducing ice crystal formation
The present invention provides peptoid polymers capable of reducing or inhibiting the formation of ice crystals at sub 0° C. temperatures. Also provided are peptoid-peptide hybrids comprising the peptoid polymers provided herein. The peptoid polymers and peptoid-peptide hybrids provided herein are useful for making cryoprotectant solutions. The peptoid polymers, peptoid-peptide hybrids, and cryoprotectant solutions provided herein are useful for making antifreeze solutions, frozen food products, and cosmetic care products. Also provided herein are methods for preserving a tissue, an organ, a cell, or a biological macromolecule using the compositions described herein.
1. A peptoid-peptide hybrid comprising:
(a) a peptoid polymer according to formula (I):
a tautomer thereof or stereoisomer thereof,
wherein:
each R 1 is independently selected from the group consisting of H, optionally substituted C 1-18 alkyl, optionally substituted C 2-18 alkenyl, optionally substituted C 2-18 alkynyl, optionally substituted C 1-18 hydroxyalkyl, optionally substituted alkoxy, optionally substituted C 1-18 alkylamino, optionally substituted C 1-18 alkylthio, optionally substituted carboxyalkyl, C 3-10 cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (C 3-10 cycloalkyl)alkyl, (heterocycloalkyl)alkyl, arylalkyl, and heteroarylalkyl,
wherein at least 2 instances of R 1 are independently selected optionally substituted C 1-18 hydroxyalkyl groups, and
wherein any of the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups is optionally and independently substituted with one or more R 3 groups;
each R 2 is independently selected from the group consisting of H, optionally substituted C 1-18 alkyl, optionally substituted C 2-18 alkenyl, optionally substituted C 2-18 alkynyl, optionally substituted C 1-18 hydroxyalkyl, optionally substituted C 1-18 alkylamino, optionally substituted C 1-18 alkylthio, and optionally substituted carboxyalkyl;
each R 3 is independently selected from the group consisting of halogen, oxo, thioxo, —OH, —SH, amino, C 1-8 alkyl, C 1-8 hydroxyalkyl, C 1-8 alkylamino, and C 1-8 alkylthio;
X and Y are independently selected from the group consisting of H, optionally substituted C 1-8 alkyl, optionally substituted C 1-8 acyl, optionally substituted C 1-8 alkylamino, —OH, —SH, —NH 2 , carboxy, optionally substituted C 1-8 hydroxyalkyl, optionally substituted C 1-8 alkylamino, optionally substituted C 2-8 alkylthio, optionally substituted C 1-8 carboxyalkyl, and halogen, or
alternatively X and Y are taken together to form a covalent bond; and
the subscript n, representing the number of peptoid monomers in the peptoid polymer, is between 8 and 50; and
(b) one or more amino acids, wherein the one or more amino acids are located at one or both ends of the peptoid polymer and/or in between any of the peptoid monomers.
2. The peptoid-peptide hybrid of claim 1 , wherein the C 1-18 hydroxyalkyl groups are independently selected optionally substituted C 1-6 hydroxyalkyl groups.
3. The peptoid-peptide hybrid of claim 1 , wherein each R 1 is independently selected from the group consisting of
wherein:
m is between 1 and 8; and
R 3 is selected from the group consisting of H, C 1-8 alkyl, halogen, hydroxyl, thiol, nitro, amine, oxo, and thioxo.
4. The peptoid-peptide hybrid of claim 3 , wherein one or more R 1 has a structure according to R 1b :
5. The peptoid-peptide hybrid of claim 1 , wherein each R 1 is independently selected from the group consisting of
6. The peptoid-peptide hybrid of claim 1 , wherein at least 4 instances of R 1 are independently selected optionally substituted C 1-18 hydroxyalkyl groups.
7. The peptoid-peptide hybrid of claim 1 , wherein each instance of R 2 is H.
8. The peptoid-peptide hybrid of claim 1 , wherein n is between 8 and 25.
9. The peptoid-peptide hybrid of claim 1 , wherein n is between 8 and 20.
10. The peptoid-peptide hybrid of claim 1 , wherein n is between 10 and 25.
11. The peptoid-peptide hybrid of claim 1 , wherein X is selected from the group consisting of H, C 1-8 alkyl, and C 1-8 acyl; and Y is selected from the group consisting of OH and amino.
12. The peptoid-peptide hybrid of claim 1 , wherein the one or more amino acids are selected from the group consisting of alanine, cysteine, aspartic acid, glutamic acid, phenylalanine, glycine, histidine, isoleucine, arginine, lysine, leucine, methionine, asparagine, proline, glutamine, serine, threonine, valine, tryptophan, tyrosine, and a combination thereof.
13. The peptoid-peptide hybrid of claim 1 , wherein the one or more amino acids are selected from the group consisting of isoleucine, leucine, serine, threonine, alanine, valine, arginine, and a combination thereof.
14. The peptoid-peptide hybrid of claim 1 , wherein the peptoid-peptide hybrid comprises between 1 and 10 amino acids.
15. The peptoid-peptide hybrid of claim 1 , wherein the peptoid-peptide hybrid comprises two or more amino acids.
16. The peptoid-peptide hybrid of claim 15 , wherein the two or more amino acids are contiguous.
17. The peptoid-peptide hybrid of claim 15 , wherein the two or more amino acids are separated by one or more peptoid monomers.
18. The peptoid-peptide hybrid of claim 1 , wherein the peptoid-peptide hybrid reduces or inhibits ice crystal formation at a temperature within about 0° C. to about −20° C.
19. The peptoid-peptide hybrid of claim 1 , wherein the peptoid-peptide hybrid reduces or inhibits ice crystal formation at a temperature within about −20° C. to about −200° C.
20. A cryoprotectant solution comprising a peptoid-peptide hybrid of claim 1 .
21. A method for preserving a tissue, organ, or cells, the method comprising contacting the tissue, organ, or cells with a peptoid-peptide hybrid of claim 1 .
22. The method of claim 21 , wherein the tissue is a bioengineered tissue.
23. The method of claim 21 , wherein the tissue or organ is selected from the group consisting of heart, liver, lung, kidney, pancreas, intestine, thymus, cornea, bone marrow, organoids, and a combination thereof.
24. The method of claim 21 , wherein the cells are selected from the group consisting of heart cells, liver cells, lung cells, kidney cells, pancreatic cells, intestinal cells, induced pluripotent stem cells, neural cells, blood cells, hematopoietic stem cells, lymphocytes, granulocytes, immune system cells, bone cells, stem cells, sperm cells, oocytes, embryonic cells, and a combination thereof.
25. The method of claim 24 , wherein the cells are human cells.
26. A method for preserving a biological macromolecule, the method comprising contacting the biological macromolecule with a peptoid-peptide hybrid of claim 1 .
27. The method of claim 26 , wherein the biological macromolecule is selected from the group consisting of a nucleic acid, an amino acid, a protein, an isolated protein, a peptide, a lipid, a composite structure, and a combination thereof.
28. A method for preserving an organ for transplantation, the method comprising contacting the organ with a peptoid-peptide hybrid of claim 1 .