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

• Published in: Amino acids Vol. 45; no. 5; pp. 1143 - 1148
• Main Authors: Qian, Wen-Jian, Burke, Terrence R., Jr
• Format: Journal Article
• Language: English
• Published: Vienna Springer-Verlag 01.11.2013; Springer Vienna; Springer Nature B.V
• Subjects: Aminobutyrates - chemistry; Analytical Chemistry; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; drugs; Life Sciences; Molecular Structure; Neurobiology; Original Article; peptides; Peptides - chemical synthesis; Peptides - chemistry; phosphorous acid; Phosphothreonine - chemistry; Prodrugs - chemical synthesis; Prodrugs - chemistry; Proteomics; Solid-Phase Synthesis Techniques; synthesis; Pmab; Signal transduction; Prodrug; Solid-phase peptide synthesis; Phosphothreonine mimetic
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-013-1567-0

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.