Realizing the promise of ‘La Dolce Vita’ via chemical biology: glycan-motif editing of sLeX for precision cancer therapeutics

Abstract

The convergence of glycochemistry and glycobiology is enabling the creation of new therapeutic approaches with unprecedented capacity to alter cell and organismic biology using strategies that can uniquely and specifically custom-modify the expression of key cell surface glycan motifs. We define this evolving field of chemical biology as ‘glycan-motif editing’, and one of the principal targets of this glycoengineering effort is the sialofucosylated terminal lactosaminyl glycan known as sLe^X (CD15s). This tetrasaccharide structure plays pivotal roles in both steady-state and malignant hematopoiesis, in regulation of the immune response, and in cancer metastasis. Within this biological framework, we discuss the immense potential of glycan-motif editing in enabling precision therapeutics that will profoundly improve outcomes for patients suffering from a wide variety of disabling and life-threatening conditions, particularly cancer.