Pharmaceutical formulations, methods for treating chemical warfare agent exposure, and modified biomolecules
Pharmaceutical formulations that can include at least one genetically modified OPH enzyme are provided. Methods for treating chemical warfare agent exposure are also provided. Modified biomolecules are also provided.
1 . A pharmaceutical formulation comprising a composition and a pharmaceutically-acceptable buffer, wherein the composition comprises:
a first organophosphorus hydrolase (OPH) protein:polymer conjugate that comprises:
at least a first genetically-modified OPH YT protein; and
at least a first polymer produced via controlled radical polymerization from a molecular initiator, wherein the molecular initiator is conjugated to the first genetically-modified OPH YT protein and the polymer comprises polyethylene glycol methyl-ethyl methacrylate (PEGMA) chain;
wherein an in vivo k cat /k m of the protein:polymer conjugate is >1×10 7 for at least one G-series chemical warfare agent.
2 . The pharmaceutical formulation of claim 1 , wherein the protein:polymer conjugate has a molecular weight in a range of 175 kDa to 222 kDa.
3 . The pharmaceutical formulation of claim 1 , wherein the formulation further comprises a second OPH protein:polymer conjugate,
wherein the second OPH protein:polymer conjugate comprises at least a second, genetically modified OPH protein, selected from the group consisting of OPH YT protein, OPH C23 protein, and OPH IVH3 protein.
4 . The pharmaceutical formulation of claim 1 , wherein the molecule initiator is N-hydroxysuccinimide-tetra-ethylene-glycol bromide (NHS-TEG-Br).
5 . A pharmaceutical formulation comprising a composition and a pharmaceutically-acceptable buffer, wherein the composition comprises:
a first organophosphorus hydrolase (OPH) protein:polymer conjugate that comprises:
at least a first genetically-modified OPH YT protein; and
at least a first polymer conjugated thereto, the polymer comprising a polyethylene glycol methyl-ethyl methacrylate (PEGMA) chain;
wherein an in vivo k cat /k m of the protein:polymer conjugate is >1×10 7 for at least one G-series chemical warfare agent.
6 . The pharmaceutical formulation of claim 1 , wherein the protein:polymer conjugate has a molecular weight in a range of 54 kDa to 130 kDa.
7 . The pharmaceutical formulation of claim 1 , wherein the protein:polymer conjugate has a molecular weight in a range of 130 kDa to 175 kDa.
8 . The pharmaceutical formulation of claim 5 , wherein the protein:polymer conjugate has a molecular weight in a range of 54 kDa to 130 kDa.
9 . The pharmaceutical formulation of claim 5 , wherein the protein:polymer conjugate has a molecular weight in a range of 130 kDa to 175 kDa.
10 . The pharmaceutical formulation of claim 5 , wherein the protein:polymer conjugate has a molecular weight in a range of 175 kDa to 222 kDa.