Butyrylcholinesterase variant polypeptides with increased catalytic efficiency and methods of use
OwnerJeffry D. Watkins, James D. Pancookinventors
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Abstract
The invention provides twenty-one butyrylcholinesterase variants having increased cocaine hydrolysis activity as well as the corresponding encoding nucleic acids. The invention further provides methods of hydrolyzing a cocaine-based butyrylcholinesterase substrate as well as methods of treating a cocaine-induced condition.
Claims54
A butyrylcholinesterase variant polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:
- 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40 and 42, or a functional fragment thereof.
A nucleic acid encoding a butyrylcholinesterase variant polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:
- 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40 and 42, or a functional fragment thereof.
A nucleic acid encoding a butyrylcholinesterase variant polypeptide comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOS:
- 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39 and 41, or a fragment thereof.
A method of treating a cocaine-induced condition comprising administering to an individual an effective amount of a butyrylcholinesterase variant polypeptide selected from the group consisting of SEQ ID NOS:
- 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40 and 42, or functional fragment thereof, exhibiting increased cocaine hydrolysis activity compared to butyrylcholinesterase.
A method of hydrolyzing a cocaine-based butyrylcholinesterase substrate comprising contacting said butyrylcholinesterase substrate with a butyrylcholinesterase variant polypeptide selected from the group consisting of SEQ ID NOS:
- 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40 and 42, or functional fragment thereof, under conditions that allow hydrolysis of cocaine into metabolites, wherein said butyrylcholinesterase variant polypeptide exhibits a two-fold or more increase in cocaine hydrolysis activity compared to butyrylcholinesterase.
A method of treating a cocaine-induced condition comprising administering to an individual an effective amount of a butyrylcholinesterase variant polypeptide selected from the group consisting of SEQ ID NOS:
- 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40 and 42, or functional fragment thereof, wherein said butyrylcholinesterase variant polypeptide exhibits a two-fold or more increase in cocaine hydrolysis activity compared to butyrylcholinesterase.
Dependencies are inferred from the claim text.