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Identification of Chemokine Ligands by Biochemical Fragmentation and Simulated Peptide Evolution
Author(s) -
Fuchs JensAlexander,
Brunner Cyrill,
Schineis Philipp,
Hiss Jan A.,
Schneider Gisbert
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201902022
Subject(s) - chemokine receptor , pharmacophore , c c chemokine receptor type 7 , ccl19 , peptide , computational biology , chemistry , antiparallel (mathematics) , chemokine , biochemistry , receptor , biology , physics , quantum mechanics , magnetic field
Short linear peptides can overcome certain limitations of small molecules for targeting protein–protein interactions (PPIs). Herein, the interaction between the human chemokine CCL19 with chemokine receptor CCR7 was investigated to obtain receptor‐derived CCL19‐binding peptides. After identifying a linear binding site of CCR7, five hexapeptides binding to CCL19 in the low micromolar to nanomolar range were designed, guided by pharmacophore and lipophilicity screening of computationally generated peptide libraries. The results corroborate the applicability of the computational approach and the chosen selection criteria to obtain short linear peptides mimicking a protein–protein interaction site.