Artificial oxygen transport protein
View Patent ↗This invention provides heme-containing peptides capable of binding molecular oxygen at room temperature. These compounds may be useful in the absorption of molecular oxygen from molecular oxygen-containing atmospheres. Also included in the invention are methods for treating an oxygen transport deficiency in a mammal.
1. A composition comprising a peptide comprising an amino acid sequence selected from the group consisting of
SEQ ID NO:1, the cystine derivative of SEQ ID NO:1,
(SEQ ID NO:2)-LOOP-(SEQ ID NO:2),
(SEQ ID NO:21)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22),
(SEQ ID NO:22)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22),
(SEQ ID NO:21)-LOOP-(SEQ ID NO:23)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22),
(SEQ ID NO:21)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:24),
SEQ ID NO:17, the homodimer of the cystine derivative of SEQ ID NO:17,
SEQ ID NO:18, the homodimer of the cystine derivative of SEQ ID NO:18,
SEQ ID NO:19, the homodimer of the cystine derivative of SEQ ID NO:19,
SEQ ID NO:20, and the homodimer of the cystine derivative of SEQ ID NO:20.
2. The composition of claim 1 , wherein each occurrence of LOOP is independently selected from the group consisting of GGSGSGSG (SEQ ID NO:3), GGSGGGSG (SEQ ID NO:4), GGSGSGSGG (SEQ ID NO:25), G GSGGSGGSGG (SEQ ID NO:26) and GGSGCGSGG (SEQ ID NO:27).
3. The composition of claim 2 , wherein said peptide comprises an amino acid sequence selected from the group consisting of (SEQ ID NO:2)-(SEQ ID NO:3)-(SEQ ID NO:2), (SEQ ID NO:2)-(SEQ ID NO:4)-(SEQ ID NO:2), SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15.
4. The composition of claim 1 , further comprising at least one heme;
wherein said peptide is bound to said at least one heme.
5. The composition of claim 4 , wherein said at least one heme is selected from the group consisting of heme A, heme B, heme C, heme O, mesohemes, deuterohemes, synthetic dicyano porphyrins and symmetrical porphyrins.
6. A method of removing oxygen gas from an oxygen gas-containing atmosphere, wherein said method comprises exposing to said oxygen gas-containing atmosphere a composition comprising:
at least one heme; and
a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, the cystine derivative of SEQ ID NO:1, (SEQ ID NO:2)-LOOP-(SEQ ID NO:2), (SEQ ID NO:22)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22), (SEQ ID NO:21)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22), (SEQ ID NO:21)-LOOP-(SEQ ID NO:23)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22), (SEQ ID NO:21)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:24), SEQ ID NO:17, the homodimer of the cystine derivative of SEQ ID NO:17, SEQ ID NO:18, the homodimer of the cystine derivative of SEQ ID NO:18, SEQ ID NO:19, the homodimer of the cystine derivative of SEQ ID NO:19, SEQ ID NO:20, and the homodimer of the cystine derivative of SEQ ID NO:20,
wherein said at least one heme is bound to said peptide.
7. The method of claim 6 , wherein said at least one heme is selected from the group consisting of heme A, heme B, heme C, heme O, mesohemes, deuterohemes, synthetic dicyano porphyrins and symmetrical porphyrins.
8. The method of claim 6 , wherein each occurrence of LOOP is independently selected from the group consisting of GGSGSGSG (SEQ ID NO:3), GGSGGGSG (SEQ ID NO:4), GGSGSGSGG (SEQ ID NO:25), G GSGGSGGSGG (SEQ ID NO:26) and GGSGCGSGG (SEQ ID NO:27).
9. The method of claim 8 , wherein said peptide comprises an amino acid sequence selected from the group consisting of (SEQ ID NO:2)-(SEQ ID NO:3)-(SEQ ID NO:2), (SEQ ID NO:2)-(SEQ ID NO:4)-(SEQ ID NO:2), SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15.
10. A method of treating an oxygen transport deficiency in a mammal in need thereof, wherein said method comprises administering to said mammal an effective amount of a composition comprising:
at least one heme; and
a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, the cystine derivative of SEQ ID NO:1, (SEQ ID NO:2)-LOOP-(SEQ ID NO:2), (SEQ ID NO:22)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22), (SEQ ID NO:21)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22), (SEQ ID NO:21)-LOOP-(SEQ ID NO:23)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22), (SEQ ID NO:21)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:22)-LOOP-(SEQ ID NO:24), SEQ ID NO:17, the homodimer of the cystine derivative of SEQ ID NO:17, SEQ ID NO:18, the homodimer of the cystine derivative of SEQ ID NO:18, SEQ ID NO:19, the homodimer of the cystine derivative of SEQ ID NO:19, SEQ ID NO:20, and the homodimer of the cystine derivative of SEQ ID NO:20,
wherein said at least one heme is bound to said peptide.
11. The method of claim 10 , wherein said at least one heme is selected from the group consisting of heme A, heme B, heme C, heme O, mesohemes, deuterohemes, synthetic dicyano porphyrins and symmetrical porphyrins.
12. The method of claim 10 , wherein each occurrence of LOOP is independently selected from the group consisting of GGSGSGSG (SEQ ID NO:3), GGSGGGSG (SEQ ID NO:4), GGSGSGSGG (SEQ ID NO:25), G GSGGSGGSGG (SEQ ID NO:26) and GGSGCGSGG (SEQ ID NO:27).
13. The method of claim 12 , wherein said peptide comprises an amino acid sequence selected from the group consisting of (SEQ ID NO:2)-(SEQ ID NO:3)-(SEQ ID NO:2), (SEQ ID NO:2)-(SEQ ID NO:4)-(SEQ ID NO:2), SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15.
14. The method of claim 10 , wherein said oxygen transport deficiency is selected from the group consisting of chronic anemia, acute anemia, sickle cell anemia, anemia associated with cancer, anemia associated with cancer chemotherapy, and anemia associated with use of radiation for cancer treatment.
15. The composition of claim 1 , further comprising a vesicle, wherein said vesicle comprises:
an amphiphilic material which is selected from the group consisting of a detergent, a phospholipid, and a combination thereof;
said at least one heme; and
said peptide,
wherein said peptide is selected from the group consisting of SEQ ID NO:17, the homodimer of the cystine derivative of SEQ ID NO:17, SEQ ID NO:18, the homodimer of the cystine derivative of SEQ ID NO:18, SEQ ID NO:19, the homodimer of the cystine derivative of SEQ ID NO:19, SEQ ID NO:20, and the homodimer of the cystine derivative of SEQ ID NO:20, and,
wherein said peptide is incorporated in the walls of said vesicle and said peptide is bound to said at least one heme.
16. A method of treating an oxygen transport deficiency in a mammal in need thereof, wherein said method comprises administering to said mammal an effective amount of a composition comprising a vesicle, wherein said vesicle comprises:
an amphiphilic material which is selected from the group consisting of a detergent, a phospholipid, and a combination thereof;
at least one heme; and
a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:17, the homodimer of the cystine derivative of SEQ ID NO:17, SEQ ID NO:18, the homodimer of the cystine derivative of SEQ ID NO:18, SEQ ID NO:19, the homodimer of the cystine derivative of SEQ ID NO:19, SEQ ID NO:20, and the homodimer of the cystine derivative of SEQ ID NO:20,
wherein said peptide is incorporated in the walls of said vesicle and said peptide is bound at said at least one heme.
17. The method of claim 16 , wherein said at least one heme is selected from the group consisting of heme A, heme B, heme C, heme O, mesohemes, deuterohemes, synthetic dicyano porphyrins and symmetrical porphyrins.
18. The method of claim 16 , wherein said oxygen transport deficiency is selected from the group consisting of chronic anemia, acute anemia, sickle cell anemia, anemia associated with cancer, anemia associated with cancer chemotherapy, and anemia associated with use of radiation for cancer treatment.
19. The method of claim 18 , wherein said mammal is human.