Patent
The present disclosures provides isolated or purified compounds, each of which bind to a metal atom. Generally, the compounds are small in size (e.g, molecular weight of less than about 1 kDa) and peptidic in nature, inasmuch as the compounds comprise amino acids. In some embodiments, the compound comprises a structure of Formula I: M 1 -P 1 -M 2 -P 2 wherein each of P 1 and P 2 is a peptide comprising at least two amino acids, M 1 is a first metal binding moiety comprising a substituted imidazolone ring, M 2 is a second metal binding moiety comprising a substituted oxazolone ring, and wherein M 1 and M 2 bind to a single metal atom. Also provided are related complexes, conjugates, cells which synthesize the compounds of the present disclosures, substantially homogenous cultures thereof, kits and compositions, and methods of making or using the materials of the present disclosures.
1. An isolated or purified compound having a molecular weight of less than 1 kDa and comprising at least four amino acids, a first metal binding moiety comprising a substituted imidazolone ring (M 1 ), and a second metal binding moiety comprising a substituted oxazolone ring (M 2 ), wherein M 1 and M 2 are linked by a dipeptide, and wherein M 1 and M 2 bind to a single metal atom.
2. The isolated or purified compound of claim 1 comprising the structure of Formula I:
M 1 -P 1 -M 2 -P 2 [Formula I]
wherein P 1 is the dipeptide linking M 1 and M 2 , P 2 is a peptide comprising at least two amino acids, M 1 is the first metal binding moiety comprising a substituted imidazolone ring, and M 2 is the second metal binding moiety-comprising a substituted oxazolone ring.
3. The isolated or purified compound of claim 2 , wherein P 2 is a dipeptide or tripeptide.
4. The isolated or purified compound of claim 2 , wherein M 1 comprises a structure of Formula IIa:
wherein R 2 comprises a side chain along with the backbone alpha-carbon of an amino acid.
5. The isolated or purified compound of claim 2 , wherein M 2 comprises a structure of Formula IIb:
wherein R 1 comprises a side chain along with the backbone nitrogen and alpha-carbon atoms of an amino acid.
6. The isolated or purified compound of claim 4 , wherein M 2 comprises the structure of Formula IIb:
wherein R 1 comprises a side chain along with the backbone nitrogen and alpha-carbon atoms of a naturally-occurring amino acid, and wherein R 2 comprises a side chain along with the alpha-carbon of a naturally-occurring amino acid, which is converted to an oxo group.
7. The isolated or purified compound of claim 4 , wherein M 2 comprises the structure of Formula IIb:
wherein R 1 comprises a side chain along with the backbone nitrogen and alpha-carbon atoms of a non-coded amino acid, wherein R 2 comprises a side chain of a non-coded amino acid, or wherein each of R 1 and R 2 comprises a side chain along with the alpha-carbon atom, which has been converted to an oxo group, of a non-coded amino acid.
8. The isolated or purified compound of claim 4 , wherein M 2 comprises the structure of Formula IIb:
wherein R 1 of Formula IIb comprises a structure of Formula III, wherein Formula III is attached as R1 to the structure of Formula IIb at the indicated attachment point:
and wherein R 3 is a hydroxyalkyl or an alkylated sulfate.
9. The isolated or purified compound of claim 8 , wherein the hydroxylalkyl is —CH(CH 3 )OH.
10. The isolated or purified compound of claim 8 , wherein the alkylated sulfate is a C1 to C4 sulfate.
11. The isolated or purified compound of claim 10 , wherein the alkylated sulfate is —CH(CH 3 )SO 4 − .
12. The isolated or purified compound of claim 4 , wherein R 2 of Formula IIa comprises an alkylated guanidinium moiety.
13. The isolated or purified compound of claim 12 , wherein R 2 of Formula IIa comprises a structure of Formula IV:
wherein n is an integer between 1 and 5.
14. The isolated or purified compound of claim 4 , wherein M 2 comprises a structure of Formula IIb
wherein R 1 comprises a structure of Formula III:
wherein R 3 is a hydroxyalkyl or an alkylated sulfate.
15. The isolated or purified compound of claim 4 , wherein M 1 comprises a structure of Formula IIa, wherein R 2 comprises a structure of Formula IV:
wherein n is an integer between 1 and 5.
16. The isolated or purified compound of claim 1 , wherein M 1 and M 2 bind to a single metal atom selected from the group consisting of Au(III), Cd(II), Co(II), Cr(VI), Cu(I), Cu(II), Fe(II), Fe(III), Hg(I), Hg(II), Ni(II), Zn(II), Ag(I), Pb(II), Pb(IV), Al(III), Mn(II), Mn(III), Mn(IV), Mn(VI), Mn(VII), U(IV), and U(VI), or a combination thereof.
17. The isolated or purified compound of claim 16 , wherein M 1 and M 2 preferentially bind to copper.
18. The isolated or purified compound of claim 2 , wherein P 2 comprises a structure of aa 3 -aa 4 or aa 3 -aa 4 -aa 5 , wherein each of aa 3 , aa 4 and aa 5 is a small aliphatic amino acid.
19. The isolated or purified compound of claim 2 , wherein P 1 comprises a structure of aa 1 -aa 2 , wherein aa 2 is a sulfur-containing amino acid or a hydroxyl-containing amino acid and aa 1 is a small aliphatic amino acid.
20. The isolated or purified compound of claim 18 , wherein the small aliphatic amino acid is selected from the group consisting of Ala, Gly, Ser, Thr, and Pro.
21. The isolated or purified compound of claim 20 , wherein each of aa 3 , and aa 4 is Ala, and aa 5 is Thr.
22. The isolated or purified compound of claim 19 , wherein aa 2 is Ser or cysteic acid.
23. The isolated or purified compound of claim 1 , comprising one of the following structures when bound to a single metal atom:
24. An isolated or purified complex comprising the compound in accordance with claim 1 , wherein M 1 and M 2 are bound to a single metal atom.
25. The isolated or purified complex of claim 24 , wherein the metal atom is selected from the group consisting of: Au(III), Cd(II), Co(II), Cr(VI), Cu(I), Cu(II), Fe(II), Fe(III), Hg(I), Hg(II), Ni(II), Zn(II), Ag(I), Pb(II), Pb(IV), Al(III), Mn(II), Mn(III), Mn(IV), Mn(VI), Mn(VII), U(IV), and U(VI) or a combination thereof.
26. The isolated or purified compound of claim 25 , wherein the metal atom is Cu(I).
27. A conjugate comprising a compound of claim 1 linked to a heterologous moiety.
28. The conjugate of claim 27 , wherein the heterologous moiety is an amino acid or peptide linked to the compound via a peptide bond.
29. The conjugate of claim 27 , wherein the heterologous moiety is a polymer.
30. A method of reducing the concentration of a metal atom from a liquid system, comprising contacting the system with the compound of claim 1 , to form complexes comprising the compound bound to the metal atom form in the system, and removing the complexes from the system.
31. The method of claim 30 , wherein the metal is selected from the group consisting of: Au(III), Cd(II), Co(II), Cr(VI), Cu(I), Cu(II), Fe(II), Fe(III), Hg(I), Hg(II), Ni(II), Zn(II), Ag(I), Pb(II), Pb(IV), ARM), Mn(II), Mn(III), Mn(IV), Mn(VI), Mn(VII), U(IV), and U(VI), or a combination thereof.
32. The method of claim 31 , wherein the metal is mercury.
33. A method of producing the complex of claim 24 comprising a metal atom, comprising incubating a solution comprising a metal atom with the compound of claim 1 .
34. The method of claim 33 , wherein the metal atom is gold, rhodium, platinum, or palladium.