Tuning probe selectivity for chemical proteomics applications

• Published in: Current opinion in chemical biology Vol. 17; no. 1; pp. 102 - 109
• Main Authors: Haedke, Ute, Küttler, Eliane V, Vosyka, Oliver, Yang, Yinliang, Verhelst, Steven HL
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2013
• Subjects: Amino Acids - analysis; Amino Acids - metabolism; Animals; Drug Discovery - methods; Humans; Molecular Imaging - methods; Molecular Probes - analysis; Molecular Probes - metabolism; Proteins - analysis; Proteins - antagonists & inhibitors; Proteins - metabolism; Proteomics - methods
• ISSN: 1367-5931; 1879-0402
• DOI: 10.1016/j.cbpa.2012.11.024

► Covalent probes enable qualitative and quantitative analysis of the proteome. ► Probe selectivity can be tuned by the reactive group and recognition element. ► Activity-based probes enable inhibitor discovery for poorly characterized enzymes. ► Imaging with covalent probes may be applied in future clinical applications. Covalent chemical probes enable investigation of a desired fraction of the proteome. It is possible to adjust the selectivity of these probes, so they either react with a certain amino acid in all proteins, a class of proteins or only a single protein species. A combination of specific reactive groups with additional recognition elements can fine tune probes to hit the desired proteins, even in the presence of related family members. Using probes of lower or higher selectivity, screening experiments for inhibitor discovery and imaging experiments for localization studies can be performed, showing only a fraction of the power of covalent small molecule probes.