Open AccessIsolating Conformers to Assess Dynamics of Peptidic Catalysts Using Computationally Designed Macrocyclic Peptides
Author(s) -
Elizabeth A Stone,
Parisa Hosseinzadeh,
Timothy W. Craven,
Michael J. Robertson,
Yaodong Han,
ShengYing Hsieh,
Anthony J. Metrano,
David C. Baker,
Scott J. Miller
Publication year - 2021
Publication title -
acs catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.898
H-Index - 198
ISSN - 2155-5435
DOI - 10.1021/acscatal.1c01097
Subject(s) - tetrapeptide , catalysis , chemistry , selectivity , conformational isomerism , molecular dynamics , combinatorial chemistry , peptide , aryl , computational chemistry , halogenation , organic chemistry , molecule , alkyl , biochemistry
Studying the relationship between catalyst conformational dynamics and selectivity in an asymmetric reaction is a challenge. In this study, cyclic peptides were computationally designed to stabilize different ground state conformations of a highly effective, flexible tetrapeptide catalyst for the atroposelective bromination of N -aryl quinazolinones. Through a combination of computational and experimental techniques, we have determined that dynamic movement of the lead catalyst plays a crucial role in achieving high enantioselectivity in the reaction of study. This approach may also serve as a valuable method for investigating the mechanism of other peptide-catalyzed transformations.