Piptides: New, Easily Accessible Chemotypes For Interactions With Biomolecules
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 04, 2021
- Source ID
- 10.1002/anie.202015203
Entities
People
- Jaru Taechalertpaisarn
- Kevin Burgess
- Maritess Arancillo
- Xiaowen Liang
Organizations
- Cancer Prevention and Research Institute of Texas
- National Institutes of Health
- National Science Foundation
- Robert A. Welch Foundation
- United States Department of Defense
- Yusuf Hamied Department of Chemistry