Eli Lilly and Company

Hybritech Incorporated

Mary S Kasher

Gary S David

Michele C Smith

Willem P Stemmer

Leslie D Anderson

Susan M Hochschwender

James A Cook

A chelating agent is covalently bonded to a biologically active molecule such as an enzyme or antibody, the biologically active molecule is contacted with a support containing a bound transition metal ion whereby the metal ion is chelated by the chelating agent and the oxidation state of the metal ion is changed by treatment with an oxidizing or a reducing agent to provide a kinetically inert: oxidation state to immobilize the biologically active molecule on the support. The transition metal ion is preferably Co(II), Cr(II) or Ru(III) and the oxidation state of the metal ion is changed to Co(III), Cr(III) or Ru(II), respectively. The chelating agent can be iminodiacetic acid, nitrilotriacetic acid, terpyridine, bipyridine, triethylenetetraamine, biethylenetriamine, 1,4,7-triazacyclonane or a chelating peptide. Certain chelating agents can immobilize more than one biologically active molecule at a metal ion site on the support. The immobilized biologically active molecules can be used in affinity chromatography or in assay systems.

Immobilization of biologically active molecules by changing the

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Indianapolis, IN, United States of America

Mary S Kasher