The alpha,alpha-difluorinated phosphonate L-pSer-analogue: an accessible chemical tool for studying kinase-dependent signal transduction.
This overview focuses on the (alpha,alpha-difluoromethylene)phosphonate mimic of phosphoserine (pCF(2)Ser) 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 PCF(2)-C bond formation. The pCF(2)-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 on 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.
Department of Chemistry, University of Nebraska, Lincoln, NE 68588, USA.
Kaushik
K
Panigrahi
MariJean
M
Eggen
Jun-Ho
JH
Maeng
Quanrong
Q
Shen
David B
DB
Berkowitz
D004002:Clodronic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008550:Melatonin / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D004002:Clodronic Acid; C041121:difluoromethylene diphosphonate; D010768:Phosphoserine; D008550:Melatonin