title: Preparation of orthogonally protected (2S, 3R)-2-amino-3-methyl-4-phosphonobutyric acid (Pmab) as a phosphatase-stable phosphothreonine mimetic and its use in the synthesis of Polo-box domain-binding peptides.
abstract: Reported herein is the first stereoselective synthesis of (2S,3R)-4-[bis-(tert-butyloxy)phosphinyl]-2-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-3-methylbutanoic acid [(N-Fmoc,O,O-(bis-(tert-butyl))-Pmab,4] as a hydrolytically-stable phosphothreonine mimetic bearing orthogonal protection compatible with standard solid-phase protocols. The synthetic approach used employs Evans' oxazolidinone for chiral induction. Also presented is the application of4in the solid-phase synthesis of polo-like kinase 1 (Plk1) polo box domain (PBD)-binding peptides. These Pmab-containing peptides retain PBD binding efficacy similar to a parent pThr containing peptide. Reagent4should be a highly useful reagent for the preparation of signal transduction-directed peptides.
authors: Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, NCI-Frederick, Frederick, MD 2170, U.S.A.
authors: Fa
authors: F
authors: Liu
authors: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, U.S.A.
authors: Jung-Eun
authors: JE
authors: Park
authors: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, U.S.A.
authors: Kyung S
authors: KS
authors: Lee
authors: Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, NCI-Frederick, Frederick, MD 2170, U.S.A.
authors: Terrence R
authors: TR
authors: Burke