Rebecca M. Wilson

A Fascinating Journey into History: Exploration of the World of Isonitriles En Route to Complex Amides

We describe herein our recent explorations in the field of isonitrile chemistry. An array of broadly useful coupling methodologies has been developed for the formation of peptidyl and glycopeptidyl amide bonds. We further describe the application of these methods to the syntheses of complex systems, including the cyclic peptide cyclosporine A, constrained peptide systems, and heterocycles.

A Vision for Vaccines Built from Fully Synthetic Tumor-Associated Antigens: From the Laboratory to the Clinic

Cancer cells may be distinguished from normal cells by cell surface displays of aberrant levels and types of carbohydrate domains. Accordingly, these tumor-associated carbohydrate antigens (TACAs) represent promising target structures for the design of anticancer vaccines. Over the past 20 years, our laboratory has sought to use the tools of chemical synthesis to develop TACA-based anticancer vaccine candidates. We provide herein a personal accounting of our laboratorys progress toward the long-standing goal of developing clinically viable fully synthetic carbohydrate-based anticancer vaccines.

On the Reach of Chemical Synthesis: Creation of a Mini-Pipeline from an Academic Laboratory

In this retrospective, we recall some select cases of synergy between very challenging chemical synthesis and the identification of promising new candidates for pharmaceutics development. The progression from targets, often referred to as small molecules, to those of a size commonly associated with biologics (including glycoproteins) is also charted.

The Winding Pathway to Erythropoietin Along the Chemistry–Biology Frontier: A Success At Last†

The total synthesis of a homogeneous erythropoietin (EPO), possessing the native amino acid sequence and chitobiose glycans at each of the three wild-type sites of N glycosylation, has been accomplished in our laboratory. We provide herein an account of our decade-long research effort en route to this formidable target compound. The optimization of the synergy of the two bedrock sciences we now call biology and chemistry was central to the success of the synthesis of EPO.

Applications of total synthesis toward the discovery of clinically useful anticancer agents

This tutorial review provides a historical sampling of synthetic efforts undertaken in our laboratory, which have led to the total syntheses of a range of small molecule natural products of potential interest in oncology. It has become evident that natural products, and structures clearly derivable from natural products, have a remarkable record in the treatment of cancer at the clinical level. It is likely that, with the growing power of chemical synthesis, small molecule natural products will play a continuing role in providing lead anticancer compounds.

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

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.