Synthesis of well defined heparan sulfate proteoglycan mimetics to study cell surface engineering and drug delivery

Abstract

Heparan sulfate proteoglycans (HSPGs) are essential components of the extracellular matrix and cell surfaces, playing pivotal roles in various biological processes. Composed of a core protein with covalently attached heparan sulfate chains, HSPGs are crucial for cell-cell interactions, signaling regulation, and the organization of the extracellular environment. The synthesis of proteoglycan mimetics involves sophisticated chemical and biochemical strategies aimed at replicating the intricate structures and functions of natural proteoglycans, such as heparan sulfate proteoglycans (HSPGs). Li et al. employ synthetic organic chemistry to design molecules that mimic the glycosaminoglycan chains (e.g., heparan sulfate, chondroitin sulfate) and the core proteins to which they attach. These mimetics are engineered to exhibit specific biological activities, such as binding to growth factors, cytokines, or cell surface receptors, similar to natural HSPGs. Bioconjugation techniques are crucial for linking synthetic glycosaminoglycan chains to appropriate protein or peptide scaffolds, ensuring structural and functional mimicry. The synthesis of proteoglycan mimetics holds significant promise for applications in regenerative medicine, drug delivery systems, and biomaterial development, where precise control over biological interactions is essential for therapeutic efficacy (Sugahara et al., 2015). Chapter 1 highlights that proteoglycans are vital components of the extracellular matrix and plasma membrane, featuring core proteins linked to glycosaminoglycans (GAGs). These complexes store and deliver growth factors, thereby regulating cellular processes. Current research is focused on creating simplified proteoglycan mimics to influence biological activities, especially in areas such as stem cell research, neural plasticity, viral inhibition, cancer biology, and biomarker development.