Detectable molecules, method of preparation and use

• US 4,843,122 A
• Filed: 04/28/1987
• Issued: 06/27/1989
• Est. Priority Date: 01/30/1984
• Status: Expired due to Term

• Current Assignee: Enzo Diagnostics, Inc.
• Original Assignee: Enzo Biochem Incorporated
• Inventors: Stavrianopoulos, Jannis G.
• Primary Examiner(s): Nucker, Christine M.
• Application Number:
  US07/043,568
• Time in Patent Office: 791 Days
• Field of Search: 534/573, 534/753, 525/61, 525/331.3, 525/333.2, 525/376, 525/453, 530/300, 530/345, 530/350, 530/402, 530/405, 536/1.1, 536/26, 536/27, 536/55.1
• US Class Current: 525/61
• CPC Class Codes: A61K 51/0497 conjugates with a carrier being an organic compounds
• CPC Class Codes: A61K 51/1093 conjugates with carriers being antibodies
• CPC Class Codes: G01N 33/533 with fluorescent label
• CPC Class Codes: G01N 33/553 Metal or metal coated

Abstract

A detectable molecule of the formula

A.sup.3 --(--X--R.sup.1 --E--Det.sup.b).sub.m

where A³ is A² or a polymer, where A³ has at least one modifiable reactive group selected from the group consisting of amino, hydroxy, cis .OH, halides, aryl, imidazoyl, carbonyl, carboxy, thiol or a residue comprising an activated carbon; --X-- is selected from the group consisting of ##STR1## a C₁ -C₁₀ branched or unbranched alkyl or aralkyl, which may be substituted by --OH; --Y-- is a direct bond to --E--, or --Y-- is --E--R² -- where R² is a C₁ -C₁₀ branched or unbranched alkyl; Z_a is chlorine, bromine or iodine; E is O, NH or an acylic divalent sulfur atom; Det^b is a chemical moiety capable of being detected, preferably comprising biotin or a metal chelator of the formula: ##STR2## or the 4-hydroxy or acyloxy derivative thereof, where R³ is C₁ -C₄ alkyl or CH₂ COOM, M is the same or different and selected from the group consisting of hydrogen, a metal or non-metal cation or is C₁ -C₁₀ alkyl, aryl or aralkyl; and m is an integer from 1 to the total number of modified reactive groups on A³. The detectable molecules are useful in in vitro or in vivo assays or therapy.

Claims

1. A compound of the formula:

##STR52## where A³ is A² or a biopolymer selected from the group consisting of an oligo- or polynucleotide, oligo- or polysaccharide, oligo- or polypeptide or a synthetic polymer, each of A² and said oligo-or polynucleotide, oligo- or polysaccharide, oligo- or polypeptide or synthetic polymer having m modifiable reactive groups consisting of amino, hydroxy, 1,2-cis diOH, halide, aryl, imidazoyl, carbonyl, carboxyl, thiol or a residue comprising an activated carbon;

Z_b is fluorine, chlorine or bromine; and

m is an integer from 1 to the total number of modifiable reactive groups on A³.

2. The compound of claim 1 wherein the biopolymer is a polypeptide which contains tyrosine, histidine or amino residues.

3. The compound of claim 1 wherein the biopolymer is a polynucleotide which contains guanine bases.

4. The compound of claim 3 wherein the polynucleotide is DNA.

5. The compound of claim 1 wherein A³ is a polypeptide or a polysaccharide.

6. The compound of claim 1 wherein said polypeptide is a structural protein, an immunoglobulin, or an enzyme.

7. The compound of claim 6 wherein said immunoglobulin is a monoclonal antibody.

8. The compound of claim 1 wherein said activated carbon in said modifiable group is present in a tyrosine or histidine residue of a polypeptide, or on a guanine, cytidine or inosine base of a polynucleotide, and is capable of covalent coupling to a diazonium compound.

9. The compound of claim 8 wherein said base is guanine.

10. The compound of claim 1 wherein A³ is a polynucleotide.

11. The compound of claim 10 wherein said polynucleotide is RNA or DNA.

12. The compound of claim 1 wherein Z_b is chlorine.

13. The compound of claim 5 wherein said reactive group is a tyrosine residue.