Peptoid-based chelating ligands for selective metal chelation
The present disclosure provides peptoid-based chelating ligands, corresponding cyclic peptoids, and methods of making thereof. Functional groups may be tailored for high metal binding affinity and selectivity. The side chains of a cyclic peptoid according to the present disclosure may be selected based on, for example, high affinity for actinide or other metal ions, selectivity for actinide or other metal ions, the ability to recover a metal once it is bound to the peptoid, and whether the overall peptoid should be hydrophobic or hydrophilic. Unlike siderophores, peptoid-based chelating ligands of the present disclosure are not readily hydrolyzed under physiological conditions. Therefore, peptoid-based chelating ligands may be, for example, used to treat actinide (e.g., iron and lead) poisoning in vivo. Moreover, peptoid-based chelating ligands of the present disclosure may be used for medical imaging, chelation therapy, drug delivery, and separation technologies, for example.
1. A method of producing a peptoid-based chelating ligand, comprising:
obtaining a peptoid backbone comprising a plurality of secondary amines, wherein at least a portion of the plurality of secondary amines is protected;
deprotecting the at least a portion of the plurality of secondary amines; and
attaching a side chain to at least a first deprotected secondary amine, the side chain comprising a functional group configured to form a coordinate bond with at least one hard cation.
2. The method of claim 1 , wherein the functional group is phosphonate, catecholate, amine, guanidinium, phosphoramidate, n-acylhydroxyamines, N-hydroxypyridone, or carbamoylmethylphosphine oxide (CMPO).
3. The method of claim 1 , wherein the at least one hard cation comprises at least one actinide.
4. The method of claim 1 , wherein the at least one hard cation comprises at least one lanthanide.
5. The method of claim 1 , wherein the side chain comprises at least one electron donor atom positioned between the peptoid backbone and the functional group, wherein the at least one electron donor atom comprises at least one of nitrogen, oxygen, or fluorine.
6. The method of claim 1 , wherein the side chain comprises at least one electron donor group comprising sulfur.
7. The method of claim 6 , wherein the at least one donor group comprising sulfur comprises at least one of a thiolate or a thiourea.
8. The method of claim 1 , further comprising:
attaching a second side chain to at least a second deprotected secondary amine, the second side chain comprising a second function group configured to form a second coordinate bond with the at least one hard cation; and
attaching a third side chain to at least a third deprotected secondary amine, the third side chain comprising a third function group configured to form a third coordinate bond with the at least one hard cation.
9. The method of claim 8 , wherein the at least one hard cation comprises a +3 charged actinide.
10. The method of claim 8 , wherein the at least one hard cation comprises a +3 charged lanthanide.
11. The method of claim 1 , wherein the peptoid backbone is cyclic.