Design and synthesis of a reagent for solid-phase incorporation of the phosphothreonine mimetic (2S,3R)-2-amino-3-methyl-4-phosphonobutyric acid (Pmab) into peptides in a bio-reversible phosphonyl-bis-pivaloyloxymethyl (POM) prodrug form

Amino Acids. 2013 Nov;45(5):1143-8. doi: 10.1007/s00726-013-1567-0. Epub 2013 Aug 2.

Abstract

Reported herein are the synthesis and solid-phase peptide incorporation of N-Fmoc-(2S,3R)-2-amino-3-methyl-4-phosphonobutyric acid bis-pivaloyloxymethyl phosphoryl ester [Fmoc-Pmab(POM)2-OH, 2] as a phosphatase-stable phosphothreonine (pThr) mimetic bearing orthogonal protection suitable for the synthesis of Pmab-containing peptides having bio-reversible protection of the phosphonic acid moiety. This represents the first report of a bio-reversibly protected pThr mimetic in a form suitable for facile solid-phase peptide synthesis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aminobutyrates / chemistry*
  • Molecular Structure
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Phosphothreonine / chemistry*
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry
  • Solid-Phase Synthesis Techniques

Substances

  • Aminobutyrates
  • Peptides
  • Prodrugs
  • Phosphothreonine
  • 2-amino-4-phosphonobutyric acid