The α,α-Difluorinated Phosphonate L-pSer-Analogue: An Accessible Chemical Tool for Studying Kinase-Dependent Signal Transduction in Vitro, and In Living Cells

Authors

Kaushik Panigrahi, University of Nebraska - Lincoln
MariJean Eggen, University of Nebraska - Lincoln
Jun-Ho Maeng, University of Nebraska - Lincoln
Quanrong Shen, University of Nebraska Medical Center
David B. Berkowitz, University of Nebraska - LincolnFollow

Date of this Version

9-25-2009

Citation

Chem Biol. 2009 September 25; 16(9): 928–936. doi:10.1016/j.chembiol.2009.08.008.

Comments

Copyright © 2009 Elsevier Ltd. All rights reserved. Used by permission.

Abstract

This overview focuses on the (α,α-difluoromethylene)phosphonate mimic of phosphoserine (pCF₂Ser) and its application to the study of kinase-mediated signal transduction – pathways of great interest to drug development. The most versatile modes of access to these chemical biological tools are discussed, organized by method of PCF₂-C bond. The pCF₂-Ser mimic may be site-specifically incorporated into peptides (SPPS) and proteins (expressed protein ligation). This isopolar, dianionic pSer mimic results in a “constitutive phosphorylation” phenotype, and is seen to support native protein-protein interactions that depend upon serine phosphorylation. Signal transduction pathways studied with this chemical biological approach include the regulation of p53 tumor suppressor protein activity, and of melatonin production. Given these successes, the future is bright for the use of such “teflon phospho-amino acid mimics” to map kinase-based signaling pathways.