Alpha-1-microglobulin derived proteins and their use
This invention relates to an alpha-1-microglobulin derived protein for medical use.
1. An alpha-1-microglobulin protein variant selected from the group of amino acid sequences consisting of:
formula I:
(SEQ ID NO: 10)
X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -X 13 -X 14 -GPVPTPPD
NIQVQENF-X 15 -ISRIYGKWYNLAIGSTCPWLKKI-X 16 -DRMTVSTLV
LGEGATEAEISMTST-X 17 -WRKGVCEETSGAYEKTDTDGKFLYHKSKW-
X 18 -ITMESYVVHTNYDEYAIFLTKKFSRHHGPTITAKLYGRAPQLRETL
LQDFRVVAQGVGIPEDSIFTMADRGECVPGEQEPEPILIPR,
and formula II:
(SEQ ID NO: 17)
X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -X 13 -X 14 -GPVPTPPDN
IQVQENF-X 15 -ISRIYGKWYNLAIGSTCPWLKKI-X 16 -DRMTVSTLVLG
EGATEAEISMTST-X 17 -WRKGVCEETSGAYEKTDTDGKFLYHKSKW-X 18 -
ITMESYVVHTNYDEYAIFLTKKFSRHHGPTITAKLYGRAPQLRETLLQDF
RVVAQGVGIPEDSIFTMADRGECVPGEQEPEPI,
wherein
at least one of X 1 -X 14 is present,
X 1 is absent or represents Met or N-formyl Met;
X 2 is absent or represents His;
X 3 is absent or represents His;
X 4 is absent or represents His;
X 5 is absent or represents His;
X 6 is absent or represents His;
X 7 is absent or represents His;
X 8 is absent or represents His;
X 9 is absent or represents His;
X 10 is absent or selected from Asp, Glu, Lys, or Arg;
X 11 is absent or selected from Asp, Glu, Lys, or Arg;
X 12 is absent or selected from Asp, Glu, Lys, or Arg;
X 13 is absent or selected from Asp, Glu, Lys, or Arg;
X 14 is absent or selected from Asp, Glu, Lys, or Arg;
X 15 represents Asp;
X 16 represents Met;
X 17 represents His;
X 18 represents Asp;
or a pharmaceutically acceptable salt thereof.
2. The alpha-1-microglobulin protein variant according to claim 1 ,
wherein
X 1 is Met,
X 2 -X 14 are absent,
X 15 is Asp,
X 16 is Met,
X 17 is His, and
X 18 is Asp.
3. The alpha-1-microglobulin protein variant according to claim 2 , having the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 18.
4. The alpha-1-microglobulin protein variant according to claim 1 ,
wherein
X 1 is Met or N-formyl Met,
X 2 -X 7 are His
X 8 and X 9 are absent,
X 10 -X 13 are Asp,
X 14 is Lys,
X 15 is Asp,
X 16 is Met,
X 17 is His, and
X 18 is Asp.
5. The alpha-1-microglobulin protein variant according to claim 4 , having the amino acid sequence of SEQ ID NO: 5 or SEQ ID NO: 20.
6. The alpha-1-microglobulin protein variant according to claim 1 , wherein
X 1 is Met or N-formyl Met,
X 2 -X 9 are His
X 10 -X 13 are Asp,
X 14 is Lys,
X 15 is Asp,
X 16 is Met,
X 17 is His, and
X 18 is Asp.
7. The alpha-1-microglobulin protein variant according to claim 6 , having the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 22.
8. The alpha-1-microglobulin protein variant according to claim 1 , wherein the protein variant is an antioxidant.
9. The alpha-1-microglobulin protein variant according to claim 1 , wherein the protein variant binds heme.
10. A pharmaceutical composition comprising an alpha-1-microglobulin protein variant according to claim 1 and one or more pharmaceutically acceptable excipients.