Claims
- 1. A crystal comprising Synagis Fab in crystalline form.
- 2. The crystal of claim 1, which is diffraction quality.
- 3. The crystal of claim 1, which is a native crystal.
- 4. The crystal of claim 1, which is a heavy-atom derivative crystal.
- 5. The crystal of claim 1, in which Synagis Fab is a mutant.
- 6. The crystal of claim 5, in which the mutant is a methionine, cystaine, selenomethionine or selenocysteine mutant.
- 7. The crystal of claim 5, in which the mutant is a conservative mutant.
- 8. The crystal of claim 5, in which the mutant is a truncated or extended mutant.
- 9. The crystal of claim 1, which is characterized by a diffraction pattern that is substantially similar to the diffraction pattern of FIG. 2.
- 10. The crystal of claim 1, which is characterized by an orthorhombic unit cell of a−77.36±0.2Å, b=103.92±0.2Å and c=68.87±0.2 Å.
- 11. The crystal of claim 1, which is produced by a method comprising the step of:
incubating a mixture in a closed container over a reservoir solution comprising a precipitant in a closed container under conditions suitable for crystallization until the crystal forms, wherein said mixture comprises a volume of a solution comprising Synagis Fab and a volume of the reservoir solution.
- 12. The crystal of claim 11 wherein the precipitant is PEG with an average molecular weight between about 3350 and about 8000.
- 13. The crystal of claim 11 wherein the precipitant is PEG with an average molecular weight of about 4000.
- 14. The crystal of claim 11, wherein the precipitant is present in a concentration between about 14% and about 20% (w/v).
- 15. The crystal of claim 11 wherein the precipitant is present in a concentration of about 15%.
- 16. The crystal of claim 11, wherein the solution further comprises between about 50 mM Tris and about 100 mM Tris.
- 17. The crystal of claim 11, wherein the solution further comprises between about 7% and about 20% 2-propanol.
- 18. The crystal of claim 11, wherein the solution further comprises about 10% 2-propanol.
- 19. The crystal of claim 11, wherein the solution has a pH of between about 6.4 and about 11.
- 20. The crystal of claim 11, wherein the solution has a pH of about 8.5.
- 21. The crystal of claim 11, which is produced by incubating the mixture comprising Synagis Fab and reservoir solution at a temperature of between about 4° C. and about 27° C.
- 22. The crystal of claim 11, which is produced by incubating the mixture comprising Synagis Fab and reservoir solution at a temperature of between about 17° C. and about 22° C.
- 23. The crystal of claim 11, which is produced by incubating the mixture comprising Synagis Fab and reservoir solution at a temperature of about 20° C.
- 24. A method of making the crystal of claim 1, comprising:
(a) mixing a volume of a solution comprising a Synagis Fab polypeptide with a volume of a reservoir solution comprising a precipitant; and (b) incubating the mixture obtained in step (a) over the reservoir solution in a closed container, under conditions suitable for crystallization until the crystal forms.
- 25. The method of claim 24, wherein the precipitant is PEG with an average molecular weight between about 3350 and about 8000.
- 26. The method of claim 24, wherein the precipitant is present in a concentration between about 14% and about 20% (w/v).
- 27. The method of claim 24, wherein the solution further comprises about 50 mM Tris.
- 28. The method of claim 24, wherein the solution further comprises between about 7% and about 20% 2-propanol.
- 29. The method of claim 24, wherein the solution has a pH of between 6.4 and about 11.
- 30. The method of claim 24, wherein the mixture comprising Synagis Fab and reservoir solution is incubated at a temperature of between about 4° C. and about 27° C.
- 31. The method of claim 24, wherein the mixture comprising Synagis Fab and reservoir solution is incubated at a temperature of between about 17° C. and about 22° C.
- 32. The method of claim 24, wherein the mixture comprising Synagis Fab and reservoir solution is incubated at a temperature of about 20° C.
- 33. A machine-readable medium embedded with information that corresponds to a three-dimensional structural representation of a crystal comprising Synagis Fab in crystalline form, or a fragment or portion thereof.
- 34. The machine readable medium of claim 33, in which the crystal is diffraction quality.
- 35. The machine readable medium of claim 33, in which the crystal is a native crystal.
- 36. The machine readable medium of claim 33, in which the crystal is a heavy-atom derivative crystal.
- 37. The machine readable medium of claim 33, in which the crystalline Synagis Fab is a mutant.
- 38. The machine readable medium of claim 37, in which the mutant is a selenomethionine or selenocysteine mutant.
- 39. The machine readable medium of claim 37, in which the mutant is a conservative mutant.
- 40. The machine readable medium of claim 37, in which the mutant is a truncated or extended mutant.
- 41. The machine-readable medium of claim 33, in which the information comprises the atomic structure coordinates Synagis Fab, or a subset thereof.
- 42. A machine-readable medium embedded with the atomic structure coordinates of Table 2, or a subset thereof.
- 43. A method of identifying a Synagis binding compound, comprising the step of using a three-dimensional structural representation of Synagis, Synagis Fab, or a fragment thereof comprising a Synagis antigen binding site, to computationally screen a candidate compound for an ability to bind the Synagis antigen binding site.
- 44. The method of claim 43 further including the steps of:
synthesizing the candidate compound; and screening the candidate compound for Synagis binding activity.
- 45. The method of claim 44 in which the structural information comprises the atomic structure coordinates of residues comprising a Synagis CDR.
- 46. The method of claim 45 in which the Synagis CDR is L1, L2, L3, H1, H2 or H3.
- 47. The method of claim 46 in which the structural information comprises the antigen binding site of Synagis.
- 48. The method of claim 47 in which the structural information comprises the Fv fragment of Synagis.
- 49. The method of claim 48 in which the structural information comprises the Fab fragment of Synagis.
- 50. A method of identifying a Synagis binding compound comprising the step of using a three-dimensional structural representation of Synagis, Synagis Fab, or a fragment thereof comprising a Synagis antigen binding site, to computationally design a synthesizable candidate compound that binds Synagis.
- 51. The method of claim 50 in which the computational design comprises the steps of:
identifying chemical entities or fragments capable of associating with the Synagis binding site; and assembling the chemical entities or fragments into a single molecule to provide the structure of the candidate compound.
- 52. The method of claim 51 further including the steps of:
synthesizing the candidate compound; and screening the candidate compound for Synagis binding activity.
- 53. The method of claim 50 in which the structural information comprises the atomic structure coordinates of residues comprising a Synagis CDR.
- 54. The method of claim 51 in which the Synagis CDR is L1, L2, L3, H1, H2 or H3.
- 55. The method of claim 52 in which the structural information comprises the antigen binding site of Synagis.
- 56. The method of claim 53 in which the structural information comprises the Fv fragment of Synagis.
- 57. The method of claim 54 in which the structural information comprises the Fab fragment of Synagis.
1. CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit under 35 U.S.C. §119 of copending provisional application No. 60/288,005, filed May 1, 2001, the content of which is hereby incorporated by reference in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60288005 |
May 2001 |
US |