Compositions and methods relating to argininosucccinate synthetase
Processes and compositions for the therapeutic treatment of pathogenic Gram-negative bacterial infection are provided whereby arginino succinate synthetase or PEGylated arginino succinate synthetase is administered to a subject to inactivate endotoxin thereby reducing the likelihood of bacterial sepsis and improving patient outcome.
1. A process of treating exposure of a subject to a bacterial endotoxin, comprising:
administering a therapeutically effective amount of argininosuccinate synthetase to a subject exposed to a bacterial endotoxin.
2. The process of claim 1 wherein said argininosuccinate synthetase is recombinantly expressed.
3. The process of claim 1 wherein said argininosuccinate synthetase is PEGylated.
4. The process of claim 1 wherein said argininosuccinate synthetase is PEGylated with a PEG comprising PEG 12 .
5. The process of claim 1 wherein said argininosuccinate synthetase is PEGylated with an unbranched PEG, a branched PEG, or combinations thereof.
6. The process of claim 5 wherein said argininosuccinate synthetase and said PEG are present in a ratio ranging from 1:1 to 1:400.
7. The process of claim 1 wherein said subject is infected with a pathogenic Gram-negative bacteria.
8. An isolated protein preparation for performing the process of claim 1 comprising:
a PEGylated argininosuccinate synthetase protein.
9. The preparation of claim 8 wherein said argininosuccinate synthetase is randomly PEGylated.
10. The preparation of claim 8 wherein said argininosuccinate synthetase is site-directed PEGylated.
11. The preparation of claim 10 wherein said argininosuccinate synthetase is site-directed PEGylated at one or more cysteines, lysines, histidines, or combinations thereof.
12. The preparation of claim 8 wherein said PEGylation comprises PEG 12 covalently associated with said argininosuccinate synthetase by an amide bond.
13. The preparation of claim 12 wherein said PEG 12 is a component of a branched PEG.
14. The preparation of claim 8 wherein said PEGylation comprises branched PEG.