Expediting Glycospace Exploration: Therapeutic Glycans via Automated Synthesis

Abstract

Glycans regulate a vast spectrum of disease-related processes, yet effectively leveraging these important mediators in a therapeutic context remains a frontier in contemporary medicine. Unlike many other classes of clinically important biopolymers, carbohydrates derive from discrete biosynthetic pathways and are not produced directly from genes. The conspicuous absence of a biological blueprint to achieve amplification creates a persistent challenge in obtaining well-defined glycostructures for therapeutic translation. Isolating purified sugars from biological sources is not without challenge, rendering synthetic organic chemistry the nexus of this advancing field. Chemical synthesis has proven to be an unfaltering pillar in the production of complex glycans, but laborious syntheses coupled with purification challenges frequently introduce reproducibility issues. In an effort to reconcile these preparative challenges with the societal importance of glycans, automated glycan synthesis was conceptualised at the start of the 21st century. This rapidly expanding, multifaceted field of scientific endeavor has effectively merged synthetic chemistry with technology and engineering to expedite the precision synthesis of target glycans. This minireview describes the structural diversity and function of glycans generated by automated glycan synthesis platforms over the last five years. The translational impact of these advances is discussed together with current limitations and future directions.