Abstract:
The human C-type lectin receptor (CLR) superfamily comprises 82 members, many of which serving as important components of the innate immune system as pathogen recognition receptors. Beyond immune surveillance, these receptors mediate essential physiological processes, including cell adhesion, migration, and differentiation. Due to their central role in pathopathology, CLRs have emerged as targets for therapeutic intervention; however, the development of high-affinity small-molecule ligands remains challenging due to the inherently shallow and polar nature of carbohydrate-binding sites. To address these limitations, we utilize glycomimetic ligands designed to mimic the structure and function of natural glycans while optimizing specificity, metabolic stability, and bioavailability. Furthermore, we explore allosteric modulation as a complementary strategy to bypass the physicochemical constraints of orthosteric carbohydrate-binding sites. This presentation will cover our multidisciplinary approaches to the rational design and chemical synthesis of glycomimetic scaffolds, our investigations into their recognition processes , and the subsequent application of these ligands for the targeted delivery of cancer immunotherapeutics.
