Chromatographic material

• US 5,240,602 A
• Filed: 04/02/1991
• Issued: 08/31/1993
• Est. Priority Date: 06/08/1987
• Status: Expired due to Fees

• Current Assignee: Chromatochem Incorporated
• Original Assignee: Chromatochem Incorporated
• Inventors: Hammen, Richard F.
• Primary Examiner(s): Therkorn, Ernest G.
• Application Number:
  US07/682,393
• Time in Patent Office: 882 Days
• Field of Search: 20/635, 20/656, 20/198.2, 20/502.1, 55/67, 55/380, 502/401, 502/402
• US Class Current: 210/198.2
• CPC Class Codes: B01D 15/3804 Affinity chromatography
• CPC Class Codes: B01J 20/289 bonded via a spacer
• CPC Class Codes: B01J 20/3204 Inorganic carriers, supports or substrates
• CPC Class Codes: B01J 20/3219 involving a particular spacer or linking group, e.g. for attaching an active group
• CPC Class Codes: B01J 20/3248 the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such
• CPC Class Codes: B01J 20/3251 comprising at least two different types of heteroatoms selected from nitrogen, oxygen or sulphur
• CPC Class Codes: B01J 20/3253 comprising a cyclic structure not containing any of the heteroatoms nitrogen, oxygen or sulfur, e.g. aromatic structures
• CPC Class Codes: B01J 20/3255 comprising a cyclic structure containing at least one of the heteroatoms nitrogen, oxygen or sulfur, e.g. heterocyclic or heteroaromatic structures
• CPC Class Codes: G01N 33/54353 with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393
• CPC Class Codes: G01N 33/552 Glass or silica

Abstract

Chromatographic material having the general formula S-B-X-Y-L where S is a solid support, B is a binding group, X is a substantially non-ionic hydrophilic organic spacer, Y is a coupling group and L is an affinity ligand. The chromatographic material is substantially free of non-specific adsorption and is stable at high pH.

Claims

1. Composition comprising material sized and dimensioned for chromatographic utility having the general formula S-B-X-Y'"'"' wherein S is a substantially non-compressible solid support comprising silica, B is a binding group containing silicon covalently linked to a silanol group of S through a siloxane bond, X is a substantially nonionic hydrophilic spacer covalently linked to B comprising polyethylene glycol having between 4 and 300 ethylene glycol units, and Y'"'"' is an activated coupling group covalently linked to X.

2. The composition of claim 1 wherein Y'"'"' is selected from the group of activated coupling groups consisting of carbonyl diimidazole, 1-methylpyridinium-2-oxide, isocyanate, 4-nitrophenyl carbonate, N-hydroxysuccinimidyl cerbaonate, trifluoroethanesulfonate, methanesulfonate, aldehyde, hydrazine, and carboxylate.

3. The composition of claim 1 wherein Y'"'"' is aldehyde.

8. The composition of claim 1, 4 or 6 wherein X has a length less than about 1200 atoms.

9. The composition of claim 1, 4 or 6 wherein X has a length less than about 100 atoms.

10. The composition of claim 1, 4 or 6 wherein said polyethylene glycol has an average molecular weight of 600 daltons or more, but not more than 300 ethylene glycol units.

11. The composition of claims 1, 4 or 6 wherein B is ##STR25## wherein R₁ is selected from OH, alkyl, substituted alkyl, alkyl oxide, and silicon oxide, and R₂ is selected from substituted alkyl, alkyl diol, alkyl ether, alkyl carboxy, alkyl thiol, and alkyloxy.

12. The composition of claim 1, 4 or 6 wherein B is ##STR26## wherein R₁ is selected from OH, alkyl, substituted alkyl, alkoxy and silicon oxide.

13. The composition of claims 1, 4 or 6 wherein the silicon of said binding group B is covalently linked to a hydrocarbon group having a length to longer than 3 carbon atoms.

4. Composition comprising material sized and dimensioned for chromatographic utility having the general formula S-B-X-Y-L wherein S is a substantially non-compressible solid support comprising silica, B is a binding group containing silicon covalently linked to a silanol group of S through a solioxane bond, X is a substantially nonionic hydrophilic spacer covalently linked to B comprising polyethylene glycol having between 4 and 300 ethylene glycol units, Y is a coupling group covalently linked to X and L is an affinity ligand covalently linked to Y.

5. The composition of claim 4 wherein Y is selected from the group consisting of ether, urethane, triazine, thiol, isothiocyanate, carboxyl, disulfide, amine, Schiff base and amide.

7. The composition of claim 4 or 6 wherein L is selected from the group consisting of boronic acid, iminodiacetic acid, guinacrine, acridine, sulfhydryl, protein A, Protein G, dinitrophenyl, cibacron blue, heparin, gelatin, concanavalin A, monoclonal and polyclonal antibodies and fragments thereof, lactine, poly (U), poly (A), lysine, 5'"'"' AMP, 2'"'"', 5'"'"' ADP, affi-gel blue, organomercurial compounds, procion red dye, biotin, avidin, calmodulin, oligo dT, triphenylmethyl, napthoyl compounds and antigens.

6. Composition comprising material having the general formula S-B-X-Y-L wherein S is a substantially non-compressible solid support comprising silica, 2 is a binding group containing silicon covalently linked to a silanol group of S through a siloxane bond, X is a substantially nonionic hydrophilic spacer covalently linked to B comprising polyethylene glycol having between 4 and 300 ethylene glycol units, Y is a coupling group covalently linked to X and L is an affinity ligand covalently linked to Y and wherein said composition has a greater specific absorption rate constant for a substance reactive with said affinity ligand L as compared to composition having the formula S-B-L.