Design and Synthesis of Glycopolypeptide and Glycolipid-based Biomaterials: Applications in Protein Delivery, Gene Transfection, and Anticoagulant Property

Padhy, Abinash (2025) Design and Synthesis of Glycopolypeptide and Glycolipid-based Biomaterials: Applications in Protein Delivery, Gene Transfection, and Anticoagulant Property. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Abinash Padhy (18IP011)) 18IP011.pdf - Submitted Version Restricted to Repository staff only Download (20MB)

Abstract

The development of biocompatible and multifunctional materials is crucial for advancing therapeutic strategies in modern medicine. Among all the biomolecules, carbohydrates are the most abundant, followed by proteins. Several conjugate materials are formed from post-translational modification of proteins such as glycosylation, phosphorylation, etc.; every material is responsible for different functions. Glycoconjugates like glycopolypeptides and glycolipids are the product of glycosylation and are actively involved in cellular signaling pathways, molecular recognition, maintaining membrane integrity, organelle trafficking, membrane transport, etc. Taking inspiration from the glycoconjugates, this doctoral thesis presents a comprehensive study on the design, synthesis, and application of glycopolypeptide- and glycolipid-based biomaterials, with a specific focus on their roles in protein delivery, gene transfection, and anticoagulant activity. Glycopolypeptides were synthesized via controlled living N-carboxyanhydride (NCA) ring-opening polymerization (ROP) technique, enabling precise control over molecular architecture and carbohydrate presentation. These biomaterials exhibited high affinity and specificity for cell surface receptors, facilitated by multivalent carbohydrate-protein interactions, and showed the potential of specific organelle targeting. The resulting glycomaterials were thoroughly characterized and evaluated for their efficacy in biological systems. Not only the macromolecules but also small amphiphilic glycolipids were synthesized to achieve targeted functional enzyme delivery without any chemical manipulation of the enzyme. Collectively, this work underscores the potential of glycopolypeptide- and glycolipid-based biomaterials as versatile platforms for biomedical applications. Hence, this thesis aims to investigate glycopolypeptide and glycolipid-based materials for an array of therapeutic solutions. We envision these findings providing valuable insights into structure-function relationships in glycomaterials and laying the groundwork for future translational research in targeted drug delivery and regenerative medicine.

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