Promising agents at the interface of biology and oncology derived through chemical synthesis

Wilson, Rebecca M.; Danishefsky, Samuel J.

doi:10.1351/pac200779122189

Pure Appl. Chem., 2007, Vol. 79, No. 12, pp. 2189-2216

http://dx.doi.org/10.1351/pac200779122189

Promising agents at the interface of biology and oncology derived through chemical synthesis*

Rebecca M. Wilson¹ and Samuel J. Danishefsky^1,2

¹ Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065, USA
² Department of Chemistry, Columbia University, Havemeyer Hall, 3000 Broadway, New York, NY 10027, USA

Abstract: This account traces the development of our synthetic glycopeptide- and glycoprotein-based research program over the past decade. We recount the syntheses of a number of biologically relevant, natural product-inspired glycopeptide constructs, including those associated with prostate specific antigen (PSA) and with the gp120 surface envelope protein of HIV. We also describe our progress toward the synthesis of the multiply glycosylated protein, erythropoietin (EPO). Particular emphasis is placed on the development of enabling methodologies which allow for the ligation of complex glycopeptide fragments, thus rendering it possible to access, through purely synthetic means, homogeneous, multidomainal glycopeptide and glycoprotein constructs.

*Invited contribution to a collection of papers for the IUPAC project 2005-042-1-300 "Chemistry for Biology". Other contributions to the project are published in this issue, pp. 2179-2366.