US 7,320,755 B2
Method of preparing ligands for hydrophobic interaction chromatography
Bo-Lennart Johansson, Uppsala (Sweden); Jean-Luc Maloisel, Uppsala (Sweden); and Nicolas Thevenin, Uppsala (Sweden)
Assigned to GE Healthcare Bio-Sciences AB, Uppsala (Sweden)
Appl. No. 10/547,570
PCT Filed Mar. 05, 2004, PCT No. PCT/SE2004/000316
§ 371(c)(1), (2), (4) Date Aug. 29, 2005,
PCT Pub. No. WO2004/078311, PCT Pub. Date Sep. 16, 2004.
Claims priority of application No. 0300612 (SE), filed on Mar. 05, 2003.
Prior Publication US 2006/0175258 A1, Aug. 10, 2006
This patent is subject to a terminal disclaimer.
Int. Cl. B01D 15/08 (2006.01)
U.S. Cl. 210—635  [210/656; 210/198.2; 210/502.1; 502/401; 502/439] 10 Claims
OG exemplary drawing
 
1. A method of preparing at least one multimodal ligand for hydrophobic interaction chromatography (HIC), which method comprises the steps of
(a) providing at least one scaffold defined by the general formula (I)

OG Complex Work Unit Drawing
wherein A, B and X irrespective of each other are carbon atoms or any heteroatoms, m is any integer between 0 and 4, and the functional group N is a nitrogen, which either replaces one X or is attached to any one of A, B and X;
(b) derivatisation of the nitrogen of the scaffold(s) with a reagent comprising a reactive group Z coupled to a residue R to introduce a primary interaction; and
(c) aminolysis of the resulting derivative to open up the cyclic structure between the carbonyl and the thiol, whereby a secondary interaction is introduced next to the carbonyl;
wherein at least one of the primary interaction and the secondary interaction comprises a hydrophobic group and wherein non of said interactions comprises ion-exchange ligands.