Open AccessApplication of High-Throughput Competition Experiments in the Development of Aspartate-Directed Site-Selective Modification of Tyrosine Residues in Peptides
Author(s) -
Alex J. Chinn,
Jaeyeon Hwang,
Byoungmoo Kim,
Craig A. Parish,
Shane W. Krska,
Scott J. Miller
Publication year - 2020
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.0c01147
Subject(s) - selectivity , tyrosine , residue (chemistry) , chemistry , peptide , aspartic acid , combinatorial chemistry , stereochemistry , surface modification , active site , biochemistry , amino acid , catalysis
Herein we report a Cu-catalyzed, site-selective functionalization of peptides that employs an aspartic acid (Asp) as a native directing motif, which directs the site of O-arylation at a proximal tyrosine (Tyr) residue. Through a series of competition studies conducted in high-throughput reaction arrays, effective conditions were identified that gave high selectivity for the proximal Tyr in Asp-directed Tyr modification. Good levels of site-selectivity were achieved in the O-arylation at a proximal Tyr residue in a number of cases, including a peptide-small molecule hybrid.