Identification and optimization of short helical peptides with novel reactive functionality as catalysts for acyl transfer by reactive tagging.
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 ∼2800-fold over background.
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA. mgagne@unc.edu mlwaters@unc.edu.
Silvia
S
Bezer
Masaomi
M
Matsumoto
Michael W
MW
Lodewyk
Stephen J
SJ
Lee
Dean J
DJ
Tantillo
Michel R
MR
Gagné
Marcey L
ML
Waters
D002384:Catalysis; D004952:Esters / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*
D004952:Esters; D010455:Peptides