Novel Chelator and Use Thereof

Patent metadata

Field	Value
Publication number	US-2018223003-A1
Application number	US-201815937428-A
Country	US
Kind code	A1
Filing date	Mar 27, 2018
Priority date	Jun 1, 2010
Publication date	Aug 9, 2018
Grant date	—

Abstract

The present invention relates to dimeric pentadentate chelators with exceptionally strong binding of metal ions, for detection, immobilization and purification of biomolecules. Dimeric chelators offer a cooperativity of binding of two adjacent immobilized metal ions simultaneously to a histidine-tagged biomolecule, which gives advantageous properties regarding strength of binding compared to a corresponding monomer chelator. In addition, a dimer increases the selectivity (ease of separation) against non-tagged biomolecules with low metal-ion affinity.

First claim

1 . A dimeric pentadentate chelator having the following general formula:

wherein Q is a solid phase, a detection label, or a biomarker,
wherein Sc is a scaffold that contains at least two functional groups that couple two pentadentate chelators (PD), wherein Sc comprises diethylenetriamine, and
wherein PD is a pentadentate chelator having the formula:

2 . The dimeric pentadentate chelator of claim 1 , wherein Q is a solid phase comprising a natural or synthetic polymer.

3 . The dimeric pentadentate chelator of claim 2 , wherein the solid phase is a porous chromatographic support.

4 . The dimeric pentadentate chelator of claim 2 , wherein Q is made of a cross-linked carbohydrate material.

5 . The dimeric pentadentate chelator of claim 4 , wherein the cross-linked carbohydrate material is agarose, agar, cellulose, dextran, chitosan, konjac, carrageenan, gellan, or alginate.

6 . The dimeric pentadentate chelator of claim 4 , wherein the cross-linked carbohydrate material is agarose.

7 . The dimeric pentadentate chelator of claim 2 , wherein Q is made of synthetic polymers such as styrene derivatives, divinylbenzene, acryl amides, acrylate esters, methacrylate esters, vinyl esters or vinyl amides.

8 . The dimeric pentadentate chelator of claim 7 , wherein the synthetic polymers comprise styrene derivatives, divinylbenzene, acryl amides, acrylate esters, methacrylate esters, vinyl esters, vinyl amides, or a combination thereof.

9 . The dimeric pentadentate chelator of claim 2 , wherein Q comprises magnetic particles.

10 . The dimeric pentadentate chelator of claim 1 , wherein Q is a solid phase comprising a sensor surface.

11 . The dimeric pentadentate chelator of claim 1 , wherein a spacer is provided between the scaffold Sc and the group Q, wherein the spacer has the following formula Xf-SP-Yf before coupling to Q and Sc, wherein Xf and Yf are selected from —OH, —SH or —OCH 2 CH═CH 2 , —CO 2 H, —NH 2 or —NH—, —N 3 , CN, OTs, OMs, Cl, Br, —CHO, —C≡CH or epoxide groups, and wherein SP is a straight or branched configuration of 2-100 atoms comprising C, N, O, S and H.

12 . The dimeric pentadentate chelator of claim 11 , wherein Xf is —CO 2 H and Yf is —SH.

13 . The dimeric pentadentate chelator of claim 11 , wherein the spacer is derived from mercapto hexanoic acid.

Assignees

• Ge Healthcare Bioprocess R&D Ab

Inventors

• Algotsson Mattias
• Andersson Lars C
• Brekkan Eggert
• Hedemyr Lee
• Maloisel Jean-Luc
• Palmgren Ronnie

Classifications

• C07C237/10

  having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups · CPC title

• B01J20/3219

  involving a particular spacer or linking group, e.g. for attaching an active group · CPC title

• C07C323/60

  with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms · CPC title

• B01J20/3251

  comprising at least two different types of heteroatoms selected from nitrogen, oxygen or sulphur · CPC title

• B01J20/3265

  with an organic functional group containing a metal, e.g. a metal affinity ligand · CPC title