IPC분류정보
국가/구분 |
United States(US) Patent
공개
|
국제특허분류(IPC7판) |
|
출원번호 |
US-0767195
(2014-02-21)
|
공개번호 |
US-0369738
(2015-12-24)
|
국제출원번호 |
PCT/US14/17735
(2014-02-21)
|
발명자
/ 주소 |
- POMPER, MARTIN G.
- WANG, HAOFAN
- MINN, IL
- LEACH, STEVEN D.
- MEASE, RONNIE C.
|
출원인 / 주소 |
- THE JOHNS HOPKINS UNIVERSITY
|
인용정보 |
피인용 횟수 :
0 인용 특허 :
0 |
초록
▼
A detectable substrate for aldehyde dehydrogenase (ALDH) can be used for selecting cells that express ALDH. The detectable substrate can have a fluorescent moiety that has an excitation wavelength, an emission wavelength, or both, that does not overlap with the excitation wavelength, emission wavele
A detectable substrate for aldehyde dehydrogenase (ALDH) can be used for selecting cells that express ALDH. The detectable substrate can have a fluorescent moiety that has an excitation wavelength, an emission wavelength, or both, that does not overlap with the excitation wavelength, emission wavelength, or both, of green fluorescent protein.
대표청구항
▼
1. A detectable substrate for ALDH comprising a compound of formula (I): wherein:m and n are each independently an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, and 8;p is an integer selected from the group consisting of 0, 1, 2, and 3;each q is independently an integer selected
1. A detectable substrate for ALDH comprising a compound of formula (I): wherein:m and n are each independently an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, and 8;p is an integer selected from the group consisting of 0, 1, 2, and 3;each q is independently an integer selected from the group consisting of 0, 1, and 2;each R1, R2, and R3 is independently selected from the group consisting of H, halogen, —OH, nitro, cyano, —O-alkyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl, or heteroaryl, optionally substituted by one to five substituents selected from H, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, —OH, —O-alkyl, nitro, cyano, aryl, or heteroaryl;R4 is selected from the group consisting of H, alkyl, alkoxyl, cycloalkyl, cycloheteroalkyl, aryl, and heteroaryl;X1 is selected from the group consisting of NR5, O, and S, wherein R5 is selected from the group consisting of H, alkyl, alkoxyl, and aryl;Y is selected from the group consisting of —CH(═O); C(═O)—O−; and —CH(OCH2CH3)2; andwherein the compound of formula (I) has a peak emission wavelength of 530 nm or greater. 2. The detectable substrate of claim 1, wherein the compound of formula (I) has the formula: 3. The detectable substrate of claim 2, wherein the compound of formula (I) is selected from the group consisting of: 4. The detectable substrate of claim 3, wherein the compound of formula (I) has the structure: 5. A method for distinguishing ALDH-expressing cells in a mixed population of cells, the method comprising: contacting the mixed population of cells with a detectable ALDH substrate of claim 1;measuring a fluorescence of the mixed population of cells; andidentifying cells exhibiting an increased fluorescence relative to a fluorescence from the mixed population of cells before being contacted with the detectable ALDH substrate. 6. The method of claim 5, wherein measuring the fluorescence includes fluorescence microscopy. 7. The method of claim 5, wherein measuring the fluorescence includes fluorescence activated cell sorting (FACS). 8. The method of claim 5, wherein at least a portion of the cells in the population express a fluorescent protein. 9. The method of claim 5, wherein the detectable ALDH substrate has a peak emission wavelength that is longer than a peak emission wavelength of a fluorescent protein, if present, by about 30 nm or more. 10. The method of claim 5, wherein the mixed population of cells is contacted with the detectable ALDH substrate in the presence of a multi-drug efflux pump inhibitor having inhibitory action against ABCB1, ABCG2, or having dual inhibitory action against both ABCB1 and ABCG2. 11. The method of claim 5, further comprising isolating the identified cells exhibiting increased fluorescence. 12. The method of claim 5, wherein the isolated cells include stem cells.
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