Piptides: New, Easily Accessible Chemotypes For Interactions With Biomolecules.
Maritess ArancilloJaru TaechalertpaisarnXiaowen LiangKevin BurgessPublished in: Angewandte Chemie (International ed. in English) (2021)
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.
Keyphrases
- growth factor
- protein protein
- small molecule
- cell death
- small cell lung cancer
- epidermal growth factor receptor
- tyrosine kinase
- living cells
- quantum dots
- cell cycle arrest
- high glucose
- diabetic rats
- public health
- image quality
- drug induced
- endothelial cells
- signaling pathway
- wound healing
- computed tomography
- magnetic resonance imaging
- binding protein