Sixty years of discoveries in glycoprotein biosynthesis and functions

Harry Schachter was at the forefront of glycobiology research for more than 60 years. His work led to the discovery of novel enzymes and pathways critical for glycoprotein biosynthesis, exploring glycan functions across various model systems and uncovering the biochemical basis of abnormal glycosylation in human disease. A dedicated mentor and role model, Schachter made groundbreaking contributions that shaped the modern glycoscience field. Central to his success were strategic collaborations with chemists who developed the specialized acceptor substrates necessary to validate his findings. These efforts notably catalyzed the creation of companies that now provide essential reference compounds to the global research community. Beyond driving biosynthetic discovery, this library of compounds enabled the synthesis of decoy molecules designed to disrupt biosynthetic processes, including potential membrane-permeable compounds with therapeutic potential. Furthermore, the development of robust glycosyltransferase assays initiated a new era of screening for core enzymes and their biosynthetic pathways. As large-scale data collection and computational modeling tools come online, the fundamental biochemical knowledge is being translated and integrated into cellular biochemical networks. This review details Schachter' s seminal work on N-glycans and mucin-type O-glycans, which established the foundation for contemporary studies of glycan function in both health and disease.