Novel thymidylate synthase mutants
OwnerLawrence Loeb, Werner Geurtseninventors
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Abstract
Novel thymidylate synthase (TS mutants) are disclosed differing from human wild type thymidylate synthase in single, double, or multiple mutations, which show enhanced resistant to TS-inhibiting drugs like 5-fluorouracil or 5-fluoro-2-deoxyuridinemonophosphate. All these mutants can be used for the protection of normal human cell populations against the toxic manifestation of analogs that inhibited TD.
Claims14
Thymidylate synthase mutants, differing from human wildtype thymidylate synthase in single mutations at positions:
- E23, T53, V84, K93, D110, D116, M190, P194, S206, M219, H250, D254, Y258 or K284,
- where further silent or nonfunctional mutations with respect to TS activity are not excluded.
Thymidylate synthase mutants differing from human wildtype thymidylate synthase in double or multiple mutations at positions:
- 55, 106, and 284;
- 5, 78, and 219;
- 45 and 254;
- 193 and 231;
- 6, 69, and 211;
- 5, 13, and 231;
- 103 and 204;
- 142 and 225;
- 17, 116, and 254;
- 117, 169, and 254;
- 120 and 278;
- 38 and 104;
- 8, 81, 131, and 230;
- 51, 82, 99, and 171;
- 167 and 192,
- where further silent or non-functional mutations with respect to TS activity are not excluded.
Dependencies are inferred from the claim text.