The α,α-Difluorinated Phosphonate L-pSer-Analogue

An Accessible Chemical Tool for Studying Kinase- Dependent Signal Transduction

Kaushik Panigrahi, MariJean Eggen, Jun Ho Maeng, Quanrong Shen, David B Berkowitz

Research output: Contribution to journalReview article

39 Citations (Scopus)

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 formation. 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 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.

Original languageEnglish (US)
Pages (from-to)928-936
Number of pages9
JournalChemistry and Biology
Volume16
Issue number9
DOIs
StatePublished - Sep 25 2009

Fingerprint

Organophosphonates
Signal transduction
Signal Transduction
Phosphotransferases
Phosphorylation
Proteins
Tumor Suppressor Protein p53
Phosphoserine
Polytetrafluoroethylene
Melatonin
Serine
Ligation
Phenotype
Amino Acids
Peptides
Ac-Nal(1)-Cpa(2)-Pal(3,6)-Arg(5)-Ala(10)-lHRH
Pharmaceutical Preparations

Keywords

  • CELLBIO
  • CHEMBIO
  • SIGNALING

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Molecular Biology
  • Clinical Biochemistry
  • Molecular Medicine
  • Pharmacology

Cite this

The α,α-Difluorinated Phosphonate L-pSer-Analogue : An Accessible Chemical Tool for Studying Kinase- Dependent Signal Transduction. / Panigrahi, Kaushik; Eggen, MariJean; Maeng, Jun Ho; Shen, Quanrong; Berkowitz, David B.

In: Chemistry and Biology, Vol. 16, No. 9, 25.09.2009, p. 928-936.

Research output: Contribution to journalReview article

Panigrahi, Kaushik ; Eggen, MariJean ; Maeng, Jun Ho ; Shen, Quanrong ; Berkowitz, David B. / The α,α-Difluorinated Phosphonate L-pSer-Analogue : An Accessible Chemical Tool for Studying Kinase- Dependent Signal Transduction. In: Chemistry and Biology. 2009 ; Vol. 16, No. 9. pp. 928-936.
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