Methods and compositions related to the modulation of riboswitches
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C12Q-001/68
C07H-021/02
C07H-021/04
C12N-005/00
출원번호
US-0158168
(2006-12-21)
등록번호
US-8313901
(2012-11-20)
국제출원번호
PCT/US2006/062494
(2006-12-21)
§371/§102 date
20090316
(20090316)
국제공개번호
WO2007/100412
(2009-09-07)
발명자
/ 주소
Breaker, Ronald R.
Blount, Kenneth F.
Puskarz, Izabela J.
Wickiser, John K.
출원인 / 주소
Yale University
대리인 / 주소
Pabst Patent Group LLP
인용정보
피인용 횟수 :
0인용 특허 :
111
초록
Disclosed herein are methods and compositions related to the detection of conformational changes and interactions with trigger molecules in riboswitches.
대표청구항▼
1. A method comprising: (a) bringing into contact a ribozyme riboswitch, a substrate labeled with a conformation dependent label and a compound, wherein the substrate is a substrate for cleavage by the ribozyme riboswitch, wherein the cleavage occurs in trans, wherein the ribozyme riboswitch is a gl
1. A method comprising: (a) bringing into contact a ribozyme riboswitch, a substrate labeled with a conformation dependent label and a compound, wherein the substrate is a substrate for cleavage by the ribozyme riboswitch, wherein the cleavage occurs in trans, wherein the ribozyme riboswitch is a glmS riboswitch; and(b) detecting change in fluorescence, wherein a change in fluorescence indicates cleavage of the substrate by the ribozyme riboswitch. 2. The method of claim 1, wherein cleavage of the substrate indicates that the compound binds to the ribozyme riboswitch. 3. The method of claim 1, wherein cleavage of the substrate indicates that the compound activates the ribozyme riboswitch. 4. The method of claim 1, wherein cleavage of the substrate indicates that the compound interacts with the ribozyme riboswitch. 5. The method of claim 1, wherein cleavage of the substrate indicates that the compound induces a conformational change in the ribozyme riboswitch. 6. The method of claim 1, wherein cleavage of the substrate indicates that the compound is a trigger molecule for the ribozyme riboswitch. 7. The method of claim 1, wherein a change in fluorescence indicates that the compound modulates substrate cleavage. 8. The method of claim 1, wherein the conformation dependent label is a Fluorescent Resonance Energy Transfer (FRET) label. 9. The method of claim 1, wherein steps (a) and (b) are performed a plurality of times in parallel using a plurality of different compounds, wherein cleavage of the substrate in the presence of one of the compounds indicates that that compound activates the ribozyme riboswitch. 10. The method of claim 9, wherein steps (a) and (b) are performed at least 20, 30, 40, 50, 75, 96, 100, 150, 200, 250, 300, 384, or 400 times in parallel. 11. The method of claim 9, wherein steps (a) and (b) are performed a plurality of times in parallel a plurality of times in sequence. 12. The method of claim 11, wherein steps (a) and (b) are performed a plurality of times in parallel at least 3, 5, 10, 15, 20, 30, 40, 50, 75, 100, 150, 200, 250, 300, or 400 times in sequence. 13. The method of claim 1, wherein the method is performed using a high throughput system. 14. The method of claim 1, wherein the ribozyme riboswitch is naturally occurring. 15. The method of claim 1, wherein the ribozyme riboswitch is engineered. 16. The method of claim 15, wherein the ribozyme riboswitch is derived from a naturally occurring ribozyme riboswitch that self-cleaves, wherein the ribozyme riboswitch is engineered by removing a segment comprising the cleavage site. 17. The method of claim 16, wherein the substrate replaces the removed segment. 18. The method of claim 15, wherein the ribozyme riboswitch is a chimera. 19. The method of claim 18, wherein the chimera comprises a riboswitch fused to a ribozyme. 20. The method of claim 19, wherein the ribozyme is derived from a ribozyme that self-cleaves, wherein a segment comprising the cleavage site of the ribozyme is removed. 21. The method of claim 20, wherein the substrate replaces the removed segment. 22. The method of claim 19, wherein the riboswitch is a guanine riboswitch. 23. The method of claim 19, wherein the ribozyme is a hammerhead ribozyme. 24. The method of claim 1, wherein the compound is a protein or peptide. 25. The method of claim 1, wherein the compound is or comprises a small organic molecule. 26. A method comprising: (a) bringing into contact a ribozyme riboswitch, a substrate labeled with a conformation dependent label and a compound, wherein a segment comprising the cleavage site is removed from the ribozyme riboswitch, wherein the ribozyme riboswitch is a glmS riboswitch and wherein the substrate is a substrate for cleavage by the ribozyme riboswitch; and(b) detecting change in fluorescence, wherein a change in fluorescence indicates cleavage of the substrate by the ribozyme riboswitch.
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