Synthesis 2014; 46(10): 1399-1406
DOI: 10.1055/s-0033-1340980
paper
© Georg Thieme Verlag Stuttgart · New York

Scalable and Cost-Effective Synthesis of a Linker for Bioconjugation with a Peptide and a Monoclonal Antibody

Javier Magano*
a  Chemical Research & Development, Pfizer Worldwide Research & Development, Eastern Point Road, Groton, CT 06340, USA   Fax: +1(860)7158593   Email: Javier.Magano@Pfizer.com
,
Brian G. Conway
a  Chemical Research & Development, Pfizer Worldwide Research & Development, Eastern Point Road, Groton, CT 06340, USA   Fax: +1(860)7158593   Email: Javier.Magano@Pfizer.com
,
Douglas Farrand
b  Analytical Research & Development, Pfizer Worldwide Research & Development, Eastern Point Road, Groton, CT 06340, USA
,
Michael Lovdahl
b  Analytical Research & Development, Pfizer Worldwide Research & Development, Eastern Point Road, Groton, CT 06340, USA
,
Mark T. Maloney
a  Chemical Research & Development, Pfizer Worldwide Research & Development, Eastern Point Road, Groton, CT 06340, USA   Fax: +1(860)7158593   Email: Javier.Magano@Pfizer.com
,
Mark J. Pozzo
c  Biotherapeutics Pharmaceutical Sciences, Pfizer Worldwide Research & Development, 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA
,
John J. Teixeira
a  Chemical Research & Development, Pfizer Worldwide Research & Development, Eastern Point Road, Groton, CT 06340, USA   Fax: +1(860)7158593   Email: Javier.Magano@Pfizer.com
,
John Rizzo
d  CovX Research, 9381 Judicial Drive, San Diego, CA 92121, USA
,
David Tumelty
d  CovX Research, 9381 Judicial Drive, San Diego, CA 92121, USA
› Author Affiliations
Further Information

Publication History

Received: 24 January 2014

Accepted after revision: 20 February 2014

Publication Date:
17 March 2014 (online)


Abstract

An efficient, scalable, and cost-effective synthesis of a linker employed in a bioconjugation process with a peptide and a monoclonal antibody is presented. Several routes were investigated that resulted in the identification of a short synthesis to a key acid intermediate from inexpensive and readily available starting materials. The final coupling of this acid with an aniline to afford the desired linker has been optimized to produce multi-gram quantities of material for clinical studies. The very limited purifications needed for both intermediates and final product make this route amenable to scale.

Supporting Information

 
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