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Piptides: New, Easily Accessible Chemotypes For Interactions With Biomolecules
Author(s) -
Arancillo Maritess,
Taechalertpaisarn Jaru,
Liang Xiaowen,
Burgess Kevin
Publication year - 2021
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.202015203
Subject(s) - epidermal growth factor receptor , biomolecule , chemotype , chemistry , phosphorylation , computational biology , epidermal growth factor , tyrosine , small molecule , intracellular , biochemistry , combinatorial chemistry , biology , receptor , chromatography , essential oil
Abstract Small molecule probe development is pivotal in biomolecular science. Research described here was undertaken to develop a non‐peptidic chemotype, piptides, that is amenable to convenient, iterative solid‐phase syntheses, and useful in biomolecular probe discovery. Piptides can be made from readily accessible pip acid building blocks and have good proteolytic and pH stabilities. An illustrative application of piptides against a protein‐protein interaction (PPI) target was explored. The Exploring Key Orientations (EKO) strategy was used to evaluate piptide candidates for this. A library of only 14 piptides contained five members that disrupted epidermal growth factor (EGF) and its receptor, EGFR, at low micromolar concentrations. These piptides also caused apoptotic cell death, and antagonized EGF‐induced phosphorylation of intracellular tyrosine residues in EGFR.