SYNTHESIS OF A TETRAVALENT CONJUGATE OF THE FIRST DOMAIN OF b2GPI: SITE SPECIFIC ATTACHMENT OF A PROTEIN TO A MULTIVALENT PLATFORM

David S. Jones*, Keith A. Cockerill, Christina A. Gamino, Jeffrey R. Hammaker, Huong-Thu Ton-Nu

La Jolla Pharmaceutical Company
6455 Nancy Ridge Drive, San Diego, CA 92121
dave.jones@ljpc.com

Abstract: The first domain of the five domain protein, b2GPI, expressed in Pichia pastoris, was site specifically modified by a transamination reaction to provide a glyoxyl group at the N-terminus. A six carbon heterobifunctional linker was prepared which contains a Boc-protected aminooxy group and a free primary amine. The linker was reacted with a tetravalent activated carbonate ester intermediate to provide a tetravalent platform with four Boc-protected aminooxy groups. The protecting groups were removed, and Transaminated Domain 1 was attached to the resultant aminooxy groups to provide a tetravalent Domain 1 conjugate by formation of oxime bonds.

Presented at the
221st ACS National Meeting
San Diego, CA
April 1-5, 2001