IP Library Granted Patent US 9,416,155
Granted Patent B2
US 9,416,155 · App. 13/515,481 · Granted Aug 16, 2016

Direct sensing of molecular species by polyfluors on a DNA backbone

Inventor: Eric Todd Kool (Stanford, CA)
Assignee: The Board of Trustees of the Leland Stanford Junior University
C07H21/00G01N31/22G01N33/582
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Quick Facts
Patent No.
US 9,416,155
App. No.
13/515,481
Granted
Aug 16, 2016
Kind
B2
Abstract

Nucleoside analogs are provided; and fluorescent sensors comprising the nucleoside analogs. The sensors comprise multiple chromophores built on a DNA backbone, in which all the natural DNA bases are replaced by excimeric or exciplex-forming fluorophores, ligands, quenchers and spacers in thousands of combinations. The sensors find use in the detection and identification of target analytes by fluorescence, e.g., detection of metal ions, neutral organic compounds and anions. The sensors find use in the detection and identification of molecular species in the vapor or gaseous phase, or the liquid phase. The sensors find use in qualitative and quantitative screening and detection methods.

Claims (27)

1. A sensor for a target analyte having the structure:

wherein A and B are each independently a backbone group, linker, or a substrate, and may be absent or present;

each X is a backbone group independently selected from a sugar-phosphate, a phosphodiester, a phosphorothioate, a phosphotriester, a locked nucleic acid (LNA) backbone group, a morpholino, a 2′-O-methyl RNA or a peptide nucleic acid backbone group;

n is 2 to 20; and

each R is independently a spacer, or one of the following structures:

wherein at least one R is a ligand for a metal ion, a quencher or a spacer, wherein the sensor lacks a natural DNA or RNA base; and

wherein the sensor binds a target analyte that is selected from a metal ion and a neutral organic molecule.

2. The sensor of claim 1 , wherein at least one R is a ligand for a metal ion.

3. The sensor of claim 1 , wherein X is ribosephosphate or deoxyribosephosphate such that the backbone groups Xn comprise a DNA or RNA backbone, and wherein R is connected to X via the C1 position of the ribose or deoxyribose.

4. The sensor of claim 1 further comprising:

at least one bound metal ion.

5. The sensor of claim 1 , whereby the fluorescence emission wavelength of the sensor changes following binding of a the target analyte.

6. The sensor of claim 1 , wherein said target analyte is a neutral organic molecule in the vapor phase.

7. The sensor of claim 2 wherein:

said target analyte is a metal ion.

8. The sensor of claim 7 wherein:

said metal ion is Zr 4+ , Hf 4+ , V 3+ , Cr 3+ , Mo 3+ , W 4+ , Mn 2+ , Ru 3+ , Os 3+ , Co 3+ , Ni 2 + , Pd 2+ , Pt 2+ , Cu 2+ , Ag + , Zn 2+ , Cd 2+ , Hg 2+ , Be 2+ , Ba 2+ , Al 3+ , In 3+ , T1 + , Ge 4+ , Sn 4+ , Pb 2+ , As 3+ , Sb 5+ , Se 4+ , Fe 2+ , Fe 3+ , Au + , Au 3+ , Te 2+ or UO 2 2+ , Li + , Na + , K + , Rb + , Cs + , Mg 2+ , Ca 2+ , Sr 2+ , La 3+ , Ce 3+ , Pr 3+ , Nd 3+ , Sm 3+ , Eu 3+ Gd 3+ , Tb 3+ , Ho 3+ , Dy 3+ , Er 3+ , Tm 3+ , Yb 3+ , Lu 3+ .

9. The sensor of claim 6 wherein:

said neutral organic molecule is a petroleum component, a petroleum additive, a sulfur compound found in oil, a cleaner/degreaser, a solvent, a polychlorinated hydrocarbon, a pesticide or a herbicide.

10. The sensor of claim 1 , wherein: said sensor is linked to a substrate through A or B.

11. A method for detection of an analyte of interest, the method comprising:

contacting a sample suspected of comprising said analyte of interest with the sensor according to claim 1 , for a time and under conditions sufficient to permit binding of said analyte of interest to said sensor; and detecting a change in fluorescence emission intensity or emission wavelength of said sensor.

12. The sensor of claim 1 , wherein n is from 2 to 8.

13. The sensor of claim 12 , wherein at least one R is selected from one of the following structures:

14. The sensor of claim 13 , wherein X is ribosephosphate or deoxyribosephosphate such that the backbone groups Xn comprise a DNA or RNA backbone, and wherein R is connected to X via the C1 position of the ribose or deoxyribose.

15. The sensor of claim 14 , wherein n is 4.

16. The sensor of claim 15 , wherein the target analyte is a neutral organic molecule in the vapor phase.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 21, 2012
From: KOOL, ERIC TODD
To: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
Reel/Frame 028822/0720 →
CONFIRMATORY LICENSE Recorded Jun 20, 2012
From: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 028407/0017 →
Continuity (2)
Provisional Application 61284210 · Dec 14, 2009
Related Publication 20120309107A1 · Dec 6, 2012