Featured Technologies
Enzymatic Tool For Installation Of Stable Thioether Crosslinks
ID U-8158
Category Biotechnology
Subcategory Manufacturing
Researchers
Brief Summary
A highly controllable, fast, and specific peptide stapling method for installation of both inter- and intra-peptide thioether crosslinks
Problem Statement
Existing solutions for installing peptide crosslinks currently require multiple steps and can typically only include a limited range of side chains. These crosslinks are commonly disulfide bonds that are redox sensitive and short lived in biological environments.
Technology Description
University of Utah researchers have developed an enzyme-based system to create more robust thioether crosslinks with a range of amino acids. This method allows for fast one-step peptide stapling and has been used to generate analogs of FDA-approved therapeutics.
Related to U-7298 and U-8159.
Benefit
- Highly controllable, fast, and specific one-step peptide stapling that occurs between native sidechains.
- Thioether crosslink is much more robust than the disulfide crosslink that is naturally found in many peptide compounds.
- Enzymatic crosslinks are fast and can be carried out at room temperature at approximately a neutral pH.
Publications
- Eastman K, Mifflin M, Oblad P, et al. (2023). A Promiscuous rSAM Enzyme Enables Diverse Peptide Cross-linking. ACS Bio Med Chem Au. 3(6): 480-493.
- Rush K, Eastman K, Kincannon W, et al. (2023). Peptide Selenocysteine Substitutions Reveal Direct Substrate-Enzyme Interactions at Auxiliary Clusters in Radical S-Adenosyl-l-methionine Maturases. J Am Chem Soc. 145(18): 10167-10177.
- Eastman K, Kincannon W, Bandarian V. (2022) Leveraging Substrate Promiscuity of a Radical S-Adenosyl-L-methionine RiPP Maturase toward Intramolecular Peptide Cross-Linking Applications. ACS Cent Sci. 8 (8): 1209-1217.
Contact Info
Jason Young
(801) 587-0519
jason.r.young@utah.edu