US 6,008,378 AGranted

Synthetic molecules that specifically react with target sequences

AssigneeThe Regents of the University of California

InventorsRoger Y. Tsien, B. Albert Griffin

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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.

Claims39

Dependent claims

A biarsenical molecule of the formula:

and tautomers, anhydrides, and salts thereof;
wherein:
each X.sup.1 or X.sup.2, independently, is Cl, Br, I, OR.sup.a, or SR.sup.a, or
X.sup.1 and X.sup.2 together with the arsenic atom form a ring having the formula ##STR12## R.sup.a is H, C.sub.1 -C.sub.4 alkyl, CH.sub.2 CH.sub.2 OH, CH.sub.2 COOH or CN;
Z is 1,2-ethanediyl, 1,2-propanediyl, 2,3-butanediyl, 1,3-propanediyl, 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;
Y.sup.1 and Y.sup.2, independently, are H or CH.sub.3 ;
or
Y.sup.1 and Y.sup.2, together form a ring such that the biarsenical molecule has the formula ##STR13## where M is O, S, CH.sub.2, C (CH.sub.3).sub.2, or NH;
R.sup.1 and R.sup.2, independently, are OR.sup.a, OAc, NR.sup.a R.sup.b, or H;
R.sup.3 and R.sup.4, independently, are H, F, Cl, Br, I, OR.sup.a, or R.sup.a ;
or
R.sup.1 together with R.sup.3, or R.sup.2 together with R.sup.4, or both, form a ring in which
(i). one of R.sup.1 or R.sup.3 is C.sub.2 -C.sub.3 alkyl and the other is NR.sup.a and
(ii). one of R.sup.2 and R.sup.4 is C.sub.2 -C.sub.3 alkyl and the other is NR.sup.a ;
R.sup.b is H, C.sub.1 -C.sub.4 alkyl, CH.sub.2 CH.sub.2 OH, CH.sub.2 COOH, or CN;
Q is CR.sup.a R.sup.b, CR.sup.a OR.sup.b, C.dbd.O, or a spirolactone having the formula:
##STR14## wherein the spiro linkage is formed at C.sub.1.

14 more elements

A kit comprising

a. a biarsenical molecule of the formula:
##STR16## and tautomers, anhydrides, and salts thereof;
wherein:
each X.sup.1 or X.sup.2, independently, is Cl, Br, I, OR.sup.a, or SR.sup.a, or
X.sup.1 and X.sup.2 together with the arsenic atom form a ring having the formula ##STR17## R.sup.a is H, C.sub.1 -C.sub.4 alkyl, CH.sub.2 CH.sub.2 OH, CH.sub.2 COOH, or CN;
Z is 1,2-ethanediyl, 1,2-propanediyl, 2,3-butanediyl, 1,3-propanediyl, 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;
Y.sup.1 and Y.sup.2, independently, are H or CH.sub.3 ;
or
Y.sup.1 and Y.sup.2, together form a ring such that the biarsenical molecule has the formula ##STR18## where M is O, S, CH.sub.2, C(CH.sub.3).sub.2, or NH;
R.sup.1 and R.sup.2, independently, are OR.sup.a, OAc, NR.sup.a R.sup.b, or H;
R.sup.3 and R.sup.4, independently, are H, F, Cl, Br, I, OR.sup.a, or R.sup.a ;
or
R.sup.1 together with R.sup.3, or R.sup.2 together with R.sub.4, or both, form a ring in which
(i). one of R.sup.1 or R.sup.3 is C.sub.2 -C.sub.3 alkyl and the other is NR.sup.a and
(ii). one of R.sup.2 and R.sup.4 is C.sub.2 -C.sub.3 alkyl and the other is NR.sup.a ;
R.sup.b is H, C.sub.1 -C.sub.4 alkyl, CH.sub.2 CH.sub.2 OH, CH.sub.2 COOH or CN;
Q is CR.sup.a R.sup.b, CR.sup.a OR.sup.b, C.dbd.O, or a spirolactone having the formula:
##STR19## wherein the Spiro linkage is formed at C.sub.1 ;
and b. a bonding partner comprising a target sequence, said target sequence comprising one or more cysteines capable of specifically reacting with said biarsenical molecule.

16 more elements

A kit comprising

a. a biarsenical molecule comprising the following formula:
##STR20## and tautomers, anhydrides, and salts thereof;
wherein:
each X.sup.1 or X.sup.2, independently, is Cl, Br, I, OR.sup.a, or SR.sup.a, or
X.sup.1 and X.sup.2 together with the arsenic atom form a ring having the formula ##STR21## R.sup.a is H, C.sub.1 -C.sub.4 alkyl, CH.sub.2 CH.sub.2 OH, CH.sub.2 COOH or CN;
Z is 1,2-ethanediyl, 1,2-propanediyl, 2,3-butanediyl, 1,3-propanediyl, 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;
Y.sup.1 and Y.sup.2, independently, are H or CH.sub.3 ;
or
Y.sup.1 and Y.sup.2, together form a ring such that the biarsenical molecule has the formula ##STR22## where M is O, S, CH.sub.2, C(CH.sub.3).sub.2, or NH;
R.sup.1 and R.sup.2, independently, are OR.sup.a, OAc, NR.sup.a R.sup.b, or H;
R.sup.3 and R.sup.4, independently, are H, F, Cl, Br, I, OR.sup.a, or R.sup.a ;
or
R.sup.1 together with R.sup.3, or R.sup.2 together with R.sup.4, or both, form a ring in which
(i). one of R.sup.1 or R.sup.3 is C.sub.2 -C.sub.3 alkyl and the other is NR.sup.a and
(ii). one of R.sup.2 and R.sup.4 is C.sub.2 -C.sub.3 alkyl and the other is NR.sup.a ;
R.sup.b is H, C.sub.1 -C.sub.4 alkyl, CH.sub.2 CH.sub.2 OH, CH.sub.2 COOH or CN;
Q is CR.sup.a R.sup.b, CR.sup.a OR.sup.b, C.dbd.O, or a spirolactone having the formula:
##STR23## wherein the spiro linkage is formed at C.sub.1 ;
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.

16 more elements

A complex comprising a biarsenical molecule and a target sequence, said target sequence comprising one or more cysteines capable of reacting with said biarsenical molecule, said biarsenical molecule having the following formula:

##STR24## and tautomers, anhydrides, and salts thereof;
wherein:
each X.sup.1 or X.sup.2, independently, is Cl, Br, I, OR.sup.a, or SR.sup.a, or
X.sup.1 and X.sup.2 together with the arsenic atom form a ring having the formula ##STR25## R.sup.a is H, C.sub.1 -C.sub.4 alkyl, CH.sub.2 CH.sub.2 OH, CH.sub.2 COOH or CN;
Z is 1,2-ethanediyl, 1,2-propanediyl, 2,3-butanediyl, 1,3-propanediyl, 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;
Y.sup.1 and Y.sup.2, independently, are H or CH.sub.3 ;
or
Y.sup.1 and Y.sup.2, together form a ring such that the biarsenical molecule has the formula ##STR26## where M is O, S, CH.sub.2, C(CH.sub.3).sub.2, or NH;
R.sup.1 and R.sup.2, independently, are OR.sup.a, OAc, NR.sup.a R.sup.b, or H;
R.sup.3 and R.sup.4, independently, are H, F, Cl, Br, I, OR.sup.a, or R.sup.a ;
or
R.sup.1 together with R.sup.3, or R.sup.2 together with R.sup.4, or both, form a ring in which
(i). one of R.sup.1 or R.sup.3 is C.sub.2 -C.sub.3 alkyl and the other is NR.sup.a and
(ii). one of R.sup.2 and R.sup.4 is C.sub.2 -C.sub.3 alkyl and the other is NR.sup.a ;
R.sup.b is H, C.sub.1 -C.sub.4 alkyl, CH.sub.2 CH.sub.2 OH, CH.sub.2 COOH or CN;
Q is CR.sup.a R.sup.b, CR.sup.a OR.sup.b, C.dbd.O, or a spirolactone having the formula:
##STR27## wherein the spiro linkage is formed at C.sub.1.

14 more elements

Dependencies are inferred from the claim text.

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Abstract