We propose to develop a novel platform technology that will produce high-affinity and high-specificity ligands to target carbohydrate binding protein (CBPs), a diverse class of proteins which possess a wide range of biological functions, playing roles cancer tumorigeneisis, immune modulation and viral infection. Our method builds upon advances in sequencing technologies and leverages the natural, low affinity, interactions of monovalent sugars for CBPs combined with the ease of synthesis of nucleic acids. Our glycan-anchored libraries will thus possess many of the attributes of nucleic acids - in particular structural rigidity, ease of synthesis and the ease with which they can be amplified and characterized - but with the enhanced chemical functionality observed in peptides, proteins and small molecule ligands. Because these reagents are based on nucleic acids, the resulting affinity agents can be readily synthesized at relatively low cost and can be easily modified with a variety of fluorophores or chemical moieties for diagnostic, therapeutic and research purposes.
There is a significant need for a low-cost, renewable, rapid and comprehensive way to find affinity reagents that can target the vast number and varied types of proteins and human disease targets being discovered. We will combine the strengths of multiple extant technologies to generate a new class of capture agents that can be readily synthesized chemically and rapidly generated in the lab. Perhaps just as importantly, these molecules will be readily amenable to chemical synthesis, providing tremendous flexibility in the range of applications in which they can be employed.
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| Kratschmer, Christina; Levy, Matthew (2018) Targeted Delivery of Auristatin-Modified Toxins to Pancreatic Cancer Using Aptamers. Mol Ther Nucleic Acids 10:227-236 |
| Trevino, Simon G; Levy, Matthew (2014) High-throughput bead-based identification of structure-switching aptamer beacons. Chembiochem 15:1877-81 |
