Saturday, December 21, 2024
12/21/2024
PROJECT SUMMARY Biomedical science relies heavily on methods for attaching ligand binding sites to proteins. Such affinity tags are essential for protein affinity purification, for improving protein solubility, and for adding functionality to proteins such as fluorescent labels or sites for chemical modification. The proposed research aims to develop a general method for modifying target proteins using affinity tags that comprise only 1-2 amino acid residues. The minimal affinity tags are bound site-specifically and with high-affinity by small (1-2 kDa) synthetic receptor that can be conjugated to solid supports and small molecules. The receptors are stable and functional in physiologic conditions, including serum, and proteins bound to these receptors can be released easily upon the addition of small molecule competitors. The proposed aims include: 1) further optimizing dipeptide recognition sites; 2) investigating the binding of synthetic receptors to target sites that already exist in protein pharmaceuticals and other bioactive peptides and proteins; 3) installing minimal affinity tags into recombinant proteins and protein pharmaceuticals; and 4) developing functional derivatives of the synthetic receptor to bring functionality to the target proteins. Such minimal affinity tags will add substantial function to target proteins while having minimal impact on their structure and activity. The proposed work builds on the rules for selective, high-affinity recognition of peptides and proteins by cucurbit[n]urils established in the undergraduate research lab of the PI. Many research groups have developed applications built on these rules, and we anticipate that the proposed research will establish a core competency that should facilitate existing biomedical applications and inspire new ones.
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