(DI)barnase-barstar complexes
A complex comprising barnase bound with high affinity to barstar, and comprising a therapeutic and/or diagnostic agent bound to barnase and/or barstar.
1. A complex comprising a Bacillus amyloliquefaciens barnase bound with high affinity to a Bacillus amyloliquefaciens barstar, and further comprising a cobalamin compound which is bound to an N-terminal end or a C-terminal end of said Bacillus amyloliquefaciens barnase or said Bacillus amyloliquefaciens barstar, wherein
said Bacillus amyloliquefaciens barnase is
(a) a polypeptide which comprises the amino acid sequence set forth in SEQ ID NO: 11; or
(b) a polypeptide which comprises at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 11; and
said Bacillus amyloliquefaciens barstar is
(a) a polypeptide which comprises the amino acid sequence set forth in SEQ ID NO: 12; or
(b) a polypeptide which comprises at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 12.
2. A complex comprising a Bacillus amyloliquefaciens dibarnase bound with high affinity to Bacillus amyloliquefaciens barstar, and further comprising cobalamin compound which is bound to an N-terminal end or a C-terminal end of said Bacillus amyloliquefaciens dibarnase or said Bacillus amyloliquefaciens barstar, wherein
said Bacillus amyloliquefaciens dibarnase comprises two units of Bacillus amyloliquefaciens barnase, each of which is, independently
(a) a polypeptide which comprises the amino acid sequence set forth in SEQ ID NO: 11; or
(b) a polypeptide which comprises at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 11; and
said Bacillus amyloliquefaciens barstar is
(a) a polypeptide which comprises the amino acid sequence set forth in SEQ ID NO: 12; or
(b) a polypeptide which comprises at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 12.
3. A pharmaceutical composition comprising the complex of claim 1 and a pharmaceutically acceptable carrier.
4. The complex according to claim 1 , wherein the polypeptide which comprises at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 12 is a polypeptide which comprises the amino acid sequence set forth in SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 or SEQ ID NO: 35.
5. The complex according to claim 1 , wherein the polypeptide which comprises at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 11 is a polypeptide which comprises the amino acid sequence set forth in SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60 or SEQ ID NO: 61.
6. The complex according to claim 2 , wherein the polypeptide which comprises at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 12 is a polypeptide which comprises the amino acid sequence set forth in SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 or SEQ ID NO: 35.
7. The complex according to claim 2 , wherein the polypeptide which comprises at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 11 is a polypeptide which comprises the amino acid sequence set forth in SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60 or SEQ ID NO: 61.
8. A pharmaceutical composition comprising the complex of claim 2 and a pharmaceutically acceptable carrier.