Zwitterionic reagents

Patent metadata

Field	Value
Publication number	US-2016274094-A1
Application number	US-201615168018-A
Country	US
Kind code	A1
Filing date	May 28, 2016
Priority date	May 21, 2010
Publication date	Sep 22, 2016
Grant date	—

Abstract

Zwitterion-containing compounds for the modification of hydrophobic molecules to improve their solubility and/or to lower their non-specific binding as provided. The zwitterion-containing compounds may be suitable for modification of detectable labels such as biotin and fluorescein to improve their solubility. The zwitterion-containing compounds may also be useful for the preparation of conjugates of proteins, peptides and other macromolecules or for crosslinking molecules and/or macromolecules.

First claim

The invention claimed is:

1 - 16 . (canceled)

17 . A zwitterion-containing compound for labeling an analyte, analyte analog, or binding partner for an analyte having the structure of formula (II):

wherein,
L 1 and L 3 , are independently selected at each occurrence from divalent C 1-20 alkyl, alkenyl, alkynyl, aryl, or aralkyl groups, each optionally substituted with up to 20 heteroatoms;
L 2 is a bond or a divalent C 1-4 alkyl, alkenyl, or alkynyl group, optionally substituted with up to 10 heteroatoms;
Z is an anion-containing group selected from the group consisting of carboxylate (—COO − ), sulfonate (—SO 3 − ), sulfate (—OSO 3 − ), phosphate (—OP(O)(OR)(O − )), and oxide (—O − ), where R is a C 1-12 alkyl, alkenyl, alkynyl, aryl, or aralkyl, optionally substituted with up to 20 heteroatoms;
Y 1 is a reactive functional group for forming covalent linkages with an analyte, analyte analog, or binding partner for an analyte, said functional group comprising a electrophilic group, nucleophilic group, or a photoreactive group;
G is a detectable label; and
R 1 is a C 1-20 alkyl, alkenyl, alkynyl, aryl, or aralkyl, optionally substituted with up to 20 heteroatoms.

18 . The zwitterion-containing compound according to claim 17 , wherein G is selected from a fluorescent label, a chemiluminescent label or biotin.

19 . The zwitterion-containing compound according to claim 18 , wherein G is fluorescein or biotin.

20 . The zwitterion-containing compound according to claim 17 , wherein Y 1 is an amine-reactive group, a thiol-reactive group, a carboxy-reactive group, a maleimidyl-reactive group, a carbohydrate-reactive group, or a photoreactive-group.

21 . The zwitterion-containing compound according to claim 20 , wherein Y 1 is selected from the group consisting of:

22 . The zwitterion-containing compound according to claim 21 , wherein Y 1 is a pentafluorophenyl (PFP) ester, maleimide, amine, or N-succinimidyloxycarbonyl.

23 . The zwitterion-containing compound according to claim 17 , wherein,
L 3 is a group —X G -R G —, where X G is attached to G, and X G is selected from a bond, oxygen, sulfur, amine, amide (—C(O)NR N — or NR N —C(O)—), ester (—C(O)—O— or —O—C(O)—), carbamate (—NR—C(O)—O— or —O—C(O)—NR N —) or urea (—NR N —C(O)NR N —), and R N is hydrogen or a C 1-20 alkyl, alkenyl, alkynyl, aryl, or aralkyl, optionally substituted with up to 20 heteroatoms; and R G is a divalent C 1-20 alkyl, alkenyl, alkynyl, aryl, or aralkyl group, optionally substituted with up to 20 heteroatoms.

24 . The zwitterion-containing compound according to claim 23 , wherein,
L 1 is selected from divalent C 1-10 alkyl groups, optionally substituted with up to 20 heteroatoms, and R G is a divalent C 1-10 alkyl, optionally substituted with up to 20 heteroatoms.

25 . The zwitterion-containing compound according to claim 24 , wherein L 1 is a divalent radical of the form —(CH 2 ) n — where n=1 to 6.

26 . The zwitterion-containing compound according to claim 24 , wherein R G is a divalent radical of the form —(CH 2 ) g — where g=1 to 6.

27 . The zwitterion-containing compound according to claim 24 , wherein L 2 is a divalent C 1-4 alkyl, optionally substituted with up to 10 heteroatoms.

28 . The zwitterion-containing compound according to claim 27 , wherein L 2 is a divalent radical of the form —(CH 2 ) m — where m=1 to 4.

29 . The zwitterion-containing compound according to claim 17 , wherein Z is sulfonate (—SO 3 − ).

30 . The zwitterion-containing compound according to claim 17 , wherein Z is phosphate (—OP(O)(OR)(O − )).

31 . The zwitterion-containing compound according to claim 17 , wherein Z is carboxylate (—COO − ).

32 . The zwitterion-containing compound according to claim 29 , having the structure:

33 . The zwitterion-containing compound according to claim 29 , having the structure:

34 . The zwitterion-containing compound according to claim 29 , having the structure:

35 . The zwitterion-containing compound according to claim 29 , having the structure:

36 . A zwitterion-containing compound for cross-linking peptides, proteins, and/or macromolecules having the structure of formula (III):
Y 1 Ω-Y 2   (III)
wherein, Ω is a zwitterion-containing group of the form

L 1 and L 4 are independently selected at each occurrence from divalent C 1-20 alkyl, alkenyl, alkynyl, aryl, or aralkyl groups, each optionally substituted with up to 20 heteroatoms;
L 2 is a bond or a divalent C 1-4 alkyl, alkenyl, alkynyl, aryl, or aralkyl group, optionally substituted with up to 10 heteroatoms;
L 5 , L 6 , and L 7 are independently selected at each occurrence from a bond or divalent C 1-20 alkyl, alkenyl, alkynyl, aryl, or aralkyl groups, each optionally substituted with up to 20 heteroatoms;
Q is selected from a carbon or nitrogen atom, and with the proviso that when Q is nitrogen, Ls, L 6 , and L 7 are each not a bond;
Z is an anion-containing group selected from the group consisting of carboxylate (—COO − ), sulfonate (—SO 3 − ), sulfate (—OSO 3 − ), phosphate (—OP(O)(OR)(O − )), and oxide (—O − ), where R is a C 1-12 alkyl, alkenyl, alkynyl, aryl, or aralkyl, optionally substituted with up to 20 heteroatoms;
Y 1 and Y 2 are independently selected at each occurrence from a reactive functional group for forming covalent linkages with a peptide, a protein, or a macromolecule comprising a electrophilic group, a nucleophilic group, or a photoreactive group; and
R 1 and R 2 are independently selected at each occurrence from C 1-20 alkyl, alkenyl, alkynyl, aryl, or aralkyl, each optionally substituted with up to 20 heteroatoms.

37 . The zwitterion-containing compound according to claim 36 , wherein Y 1 and Y 2 are independently selected at each occurrence from an amine-reactive group, a thiol-reactive group, a carboxy-reactive group, a maleimidyl-reactive group, a carbohydrate-reactive group, or a photoreactive-group.

38 . The zwitterion-containing compound according to claim 37 , wherein Y 1 and Y 2 are independently selected at each occurrence from the group consisting of:

39 . The zwitterion-containing compound according to claim 38 , wherein Y 1 or Y 2 is, at one occurrence, a pentafluorophenyl (PFP) ester, maleimide, amine, or N-succinimidyloxycarbonyl.

40 . The zwitterion-containing compo

Assignees

• Siemens Healthcare Diagnostics Inc

Inventors

• Natrajan Anand
• Sharpe David
• Wen David
• Jiang Qingping

Classifications

• A61K47/545

  Heterocyclic compounds (A61K47/558 takes precedence) · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07C309/14

  containing amino groups bound to the carbon skeleton · CPC title

• C07F9/091

  with hydroxyalkyl compounds with further substituents on alkyl · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title