title: Microwave-assisted synthesis of cyclic phosphopeptide on solid support.
abstract: Phosphopeptides are important tools for studying intracellular signal transduction events in vitro and in vivo and are also potential drugs due to their direct competition with phosphoprotein recognition elements. Cyclization has been demonstrated to improve peptide selectivity, metabolic stability, and bioavailability. However, cyclic phosphopeptide synthesis may not be straightforward due to the sterically hindered phosphorylated side-chain amino acid derivatives. One option to overcome this hurdle is to use microwave-assisted synthesis, which has been shown to increase efficiency and reduce synthesis time. Herein, a detailed protocol is provided for synthesizing cyclic phosphopeptides using automated microwave. The overall synthesis duration was reduced and yields increased compared with a manual conventional method. This method provides a general, fast and facile way to synthesize cyclic peptides, demonstrating the synthesis of cyclic phosphorylated peptides which are known to be among the most challenging to produce.
authors.affiliation: Department of Chemical and Systems Biology, School of Medicine, Stanford University, Stanford, CA, 94305-5174, USA.
authors.forename: Nir
authors.initials: N
authors.lastname: Qvit
mesh_terms: D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D008872:Microwaves; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism; D010456:Peptides, Cyclic / Q000032:analysis / Q000138:chemical synthesis* / Q000378:metabolism; D010748:Phosphopeptides / Q000032:analysis / Q000138:chemical synthesis* / Q000378:metabolism; D055550:Protein Stability; D060327:Solid-Phase Synthesis Techniques; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D016328:NF-kappa B; D010456:Peptides, Cyclic; D010748:Phosphopeptides
keywords: cyclic phosphopeptide; cyclization; inhibitor kappa B; microwave-assisted synthesis; nuclear factor-kappa B; peptide synthesis; phosphopeptide; phosphor-amino acid