Synthesis of granulocyte–macrophage colony-stimulating factor as homogeneous glycoforms and early comparisons with yeast cell-derived material

Significance As biologically active glycoproteins are increasingly investigated as potential therapeutic agents, there is a growing demand for the development of strategies for the synthesis of homogeneous, single-glycoform constructs for the purposes of rigorous evaluation. Currently, most glycoproteins are accessed through recombinant methods as complex mixtures of glycoforms. Granulocyte–macrophage colony-stimulating factor (GM-CSF) is an important glycoprotein therapeutic, used to stimulate the immune system following bone-marrow transplant and chemotherapy. GM-CSF is also being explored as a potential immunoadjuvant for anticancer vaccines. We have completed a chemical synthesis of homogeneous, single-glycoform GM-CSF. Through adaptation of this modular synthetic route, it will be possible to gain access to a menu of single-glycoform GM-CSF congeners for a wide range of biological studies.