Identification and Optimization of Short Helical Peptides with Novel Reactive Functionality as Catalysts for Acyl Transfer by Reactive Tagging
Abstract
Herein we describe the screening and subsequent optimization of peptide catalysts for ester activation. A combinatorial methodology using dye-tagged substrate analogs is described for determining which components of a His-containing helical library display acyl transfer activity. We found that helical peptides display high activity, and amino acids that reinforce this propensity are advantaged. Through this approach two new structural motifs have been discovered that are capable of activating esters in organic solvents. Unlike most acyl transfer catalysts functioning in organic solvents, these catalysts are histidine- rather than N-alkyl histidine-based. Longer peptides with localization of reactive groups on the C-terminal end of the peptide were found to further enhance catalytic activity up to approximately 2800-fold over background.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 21, 2014
- Accession Number
- ADA625776
Entities
People
- Dean J Tantillo
- Marcey L. Waters
- Masaomi Matsumoto
- Michael W. Lodewyk
- Michel R Gagné
- Silvia Bezer
- Stephen J. Lee
Organizations
- University of North Carolina at Chapel Hill