Synthetic molecules that specifically react with target sequences
AssigneeThe Regents of the University of California
InventorsRoger Y. Tsien, B. Albert Griffin
Life of this patent
Estimating the term…
Abstract
The present invention features biarsenical molecules. Target sequences that specifically react with the biarsenical molecules are also included. The present invention also features kits that include biarsenical molecules and target sequences. Tetraarsenical molecules are also featured in the invention.
Claims22
A biarsenical molecule of general formula:
- and tautomers, anhydrides, and salts thereof;
- wherein
- each X1 or X2, independently, is Cl, Br, I, ORa, or SRa, or
- X1 and X2 together with the arsenic atom form a ring having the formula:
- Ra is H, C1-C4 alkyl, CH2 CH2OH, CH2COOH or CN;
- Z is 1,2-ethanediyl, 1,2-benzenediyl, 4-methyl-1,2-benzenediyl, 1,2-cyclopentanediyl, 1,2-cyclohexanediyl, 3-hydroxy-1,2-propanediyl, 3-sulfo-1,2-propanediyl, or 1,2-bis(carboxy)-1,2-ethanediyl;
- Y1 and Y2, independently, are H or CH3;
- or
- Y1 and Y2, together form a ring such that the biarsenical molecule has the formula:
- where M is O, S, CH2, C(CH3)2, or NH;
- R1 and R2, independently, are ORa, OAc, NRaRb, or H;
- R3 and R4, independently, are H, F, Cl, Br, I, ORa, or Ra;
- or
- R1 together with R3, or R2 together with R4, or both, form a ring in which
- (i) one of R1 or R3 is C2-C3 alkyl and the other is NRa and
- (ii) one of R2 and R4 is C2-C3 alkyl and the other is NRa;
- Rb is H, C1-C4 alkyl, CH2CH2OH, CH2COOH or CN;
- Q is CRaRb, CRaORb, C═O, or a spirolactone having the formula:
- wherein the spiro linkage is formed at C1, and
- wherein said molecule is substituted at one or more positions with a detectable group wherein said detectable group is selected from the group consisting of a fluorescent group, a luminescent group, spin label, photosensitizer group for singlet oxygen generation, photocleavable moiety, chelating center, heavy atom, radioactive isotope, isotope detectable by nuclear magnetic resonance and a paramagnetic atom.
A biarsenical molecule having a luminescent detectable group, wherein said biarsenical molecule has the following formula,
- wherein Ln is Tb or Eu.
A biarsenical molecule comprising a detectable group comprising a photosensitizer group for singlet oxygen generation, wherein said biarsenical molecule has the following formula,
A biarsenical molecule comprising a detectable group comprising a chelating center, wherein said biarsenical molecule has the following formula,
A biarsenical molecule comprising a detectable group comprising a heavy atom, wherein said biarsenical molecule has the following formula,
- wherein R3═R4═I or TlOH.
A biarsenical molecule comprising a detectable group comprising a radioactive isotope, wherein said biarsenical molecule has the following formula,
- wherein R3═R4═3H or 125-I.
A biarsenical molecule comprising a detectable group comprising an isotope detectable by nuclear magnetic resonance, wherein said biarsenical molecule has the following formula,
- wherein F is 19F.
A biarsenical molecule comprising a detectable group comprising a paramagnetic atom, wherein said biarsenical molecule has the following formula,
A biarsenical molecule of general formula,
- and tautomers, anhydrides, and salts thereof
- wherein
- each X1 or X2, independently, is Cl, Br, I, ORa, or SRa, or
- X1 and X2 together with the arsenic atom form a ring having the formula:
- Ra is H, C1-C4 alkyl, CH2 CH2OH, CH2COOH or CN;
- Z is 1,2-ethanediyl, 1,2-benzenediyl, 4-methyl-1,2-benzenediyl, 1,2-cyclopentanediyl, 1,2-cyclohexanediyl, 3-hydroxy-1,2-propanediyl, 3-sulfo-1,2-propanediyl, or 1,2-bis(carboxy)-1,2-ethanediyl;
- Y1 and Y2, independently, are H or CH3;
- or
- Y1 and Y2, together form a ring such that the biarsenical molecule has the formula:
- where M is O, S, CH2, C(CH3)2, or NH.
A kit comprising,
- a) a biarsenical molecule comprising the following formula:
- and tautomers, anhydrides, and salts thereof;
- wherein
- each X1 or X2, independently, is Cl, Br, I, ORa, or SRa, or
- X1 and X2 together with the arsenic atom form a ring having the formula:
- Ra is H, C1-C4 alkyl, CH2 CH2OH, CH2COOH or CN;
- Z is 1,2-ethanediyl, 1,2-benzenediyl, 4-methyl-1,2-benzenediyl, 1,2-cyclopentanediyl, 1,2-cyclohexanediyl, 3-hydroxy-1,2-propanediyl, 3-sulfo-1,2-propanediyl, or 1,2-bis(carboxy)-1,2-ethanediyl;
- Y1 and Y2, independently, are H or CH3;
- or
- Y1 and Y2, together form a ring such that the biarsenical molecule has the formula:
- where M is O, S, CH2, C(CH3)2, or NH, and
- b) a vector comprising a nucleic acid sequence encoding a target sequence, said target sequence comprising one or more cysteines capable of specifically reacting with said biarsenical molecule.
A kit comprising,
- a) a biarsenical molecule comprising the following formula:
- and tautomers, anhydrides, and salts thereof
- wherein
- each X1 or X2, independently, is Cl, Br, I, ORa, or SRa, or
- X1 and X2 together with the arsenic atom form a ring having the formula:
- Ra is H, C1-C4 alkyl, CH2 CH2OH, CH2COOH or CN;
- Z is 1,2-ethanediyl, 1,2-benzenediyl, 4-methyl-1,2-benzenediyl, 1,2-cyclopentanediyl, 1,2-cyclohexanediyl, 3-hydroxy-1,2-propanediyl, 3-sulfo-1,2-propanediyl, or 1,2-bis(carboxy)-1,2-ethanediyl;
- Y1 and Y2, independently, are H or CH3;
- or
- Y1 and Y2, together form a ring such that the biarsenical molecule has the formula:
- where M is O, S, CH2, C(CH3)2, or NH, and
- b) a bonding partner.
Dependencies are inferred from the claim text.