Claims
- 1. A method for screening a peptoid for effectiveness in transfecting a cell with an oligonucleotide, the method comprising:
providing a plurality of different-sequence peptoids in separated compartments; forming a peptoid-oligonucleotide mixture in at least one of said compartments; contacting said mixture with a cell; and determining the degree of transfection of said cell by said oligonucleotide.
- 2. The method of claim 1, further comprising identifying a transfecting peptoid contacted with a transfected cell.
- 3. The method of claim 1, wherein said peptoids are supported on solid particles.
- 4. The method of claim 3, wherein each of said compartments contains a single particle, and each such particle has bound thereto same-sequence peptoids.
- 5. The method of claim 4, further comprising the step of releasing the peptoids from the particle in said at least one compartment, prior to forming said peptoid-oligonucleotide mixture.
- 6. The method of claim 1, wherein said oligonucleotide is an antisense oligonucleotide directed against a gene product in said cell, and said determining comprises detecting an alteration in the level of expression of said gene.
- 7. The method of claim 1, wherein said different-sequence peptoids have the general formula I:
- 8. The method of claim 7, wherein in formula I, Ra comprises a lipid moiety, and Rc is selected from —NH2, —NHR, and —NH(C═O)R, where R is lower alkyl.
- 9. The method of claim 8, wherein said lipid moiety is a sterol.
- 10. The method of claim 7, wherein in formula I, each of R1 and R2 is hydrogen.
- 11. The method of claim 7, wherein in formula I, at least one Rb includes a group which is cationic at physiologically relevant pH, and at least one Rb is uncharged at physiologically relevant pH.
- 12. The method of claim 11, wherein said cationic group is selected from aminoalkyl, ammonium, guanidino, amidino, imidazolium, pyridinium, and cationic sidechains found on naturally occurring amino acids.
- 13. A method of screening a library of different-sequence peptoids for effectiveness in transfecting a cell with an oligonucleotide, the method comprising:
(i) contacting each member of the library with an oligonucleotide, to form a plurality of peptoid-oligonucleotide mixtures, (ii) contacting each said mixture with a cell; (iii) screening each cell for transfection of the oligonucleotide; and (iv) identifying transfecting peptoids in mixtures contacted with transfected cells.
- 14. The method of claim 13, wherein said library of peptoids is provided in an array of physically separated compartments.
- 15. The method of claim 13, wherein said peptoids are supported on solid particles.
- 16. The method of claim 15, further comprising the step of releasing the peptoids from the particles in said compartments, prior to said contacting step (i).
- 17. The method of claim 15, wherein each compartment contains a single particle, and each particle contains a single peptoid.
- 18. The method of claim 16, wherein, prior to contacting step (i), a duplicate array of said library of peptoids is created.
- 19. The method of claim 18, wherein identifying step (iv) comprises identifying peptoids in said duplicate array at positions corresponding to transfecting peptoids.
- 20. The method of claim 19, wherein said identifying is done by tandem mass spectrometry (MS-MS).
- 21. The method of claim 13, wherein said cells comprise distinct cell types, and said identifying is effective to identify peptoids capable of selectively delivering oligonucleotides to a selected cell type relative to a non-selected cell type.
- 22. The method of claim 21, wherein said selected cell type is a tumor cell, and said non-selected cell type is a non-tumor cell.
- 23. The method of claim 21, wherein said selected cell type is an endothelial cell, and said non-selected cell type is an epithelial cell.
- 24. The method of claim 13, wherein said different-sequence peptoids have the general formula I:
- 25. The method of claim 24, wherein in formula I, Ra comprises a lipid moiety, and Rc is selected from —NH2, —NHR, and —NH(C═O)R, where R is lower alkyl.
- 26. The method of claim 25, wherein said lipid moiety is a sterol.
- 27. The method of claim 24, wherein in formula I, each of R1 and R2 is hydrogen.
- 28. The method of claim 24, wherein in formula I, at least one Rb includes a group which is cationic at physiologically relevant pH, and at least one Rb is uncharged at physiologically relevant pH.
- 29. The method of claim 28, wherein said cationic group is selected from aminoalkyl, ammonium, guanidino, amidino, imidazole, pyridinium, and cationic sidechains found on naturally occurring amino acids.
- 30. A method of determining the sequence of an analyte peptoid by tandem mass spectrometry, wherein the N-substituents on said peptoid are selected from a known population of substituents, comprising:
determining predicted molecular weights of fragments that would be produced by cleaving amide bonds in at least one theoretical peptoid, having a sequence based on one combination of said known population of N-substituents; subjecting the analyte peptoid to MS-MS fragmentation to produce a population of analyte fragment ions of various molecular weights; and determining whether the molecular weights of said analyte fragments correspond to said predicted molecular weights.
- 31. The method of claim 30, wherein predicted molecular weights of fragments are determined for a plurality of theoretical peptoids, having sequences based on different combinations of said known population of N-substituents.
- 32. The method of claim 31, wherein the N-substituents at one or more selected positions in the analyte peptoid are predetermined.
Parent Case Info
[0001] This application claims priority to U.S. provisional application serial No.60/257,975, filed on Dec. 23, 2000, and U.S. provisional application serial No.60/329,185 filed on Oct. 11, 2001, both of which are hereby incorporated by reference in their entirety.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60329185 |
Oct 2001 |
US |
|
60257975 |
Dec 2000 |
US |