title: Fmoc-Sec(Xan)-OH: synthesis and utility of Fmoc selenocysteine SPPS derivatives with acid-labile sidechain protection.
abstract: We report here the synthesis of the first selenocysteine SPPS derivatives which bear TFA-labile sidechain protecting groups. New compounds Fmoc-Sec(Xan)-OH and Fmoc-Sec(Trt)-OH are presented as useful and practical alternatives to the traditional Fmoc-Sec-OH derivatives currently available to the peptide chemist. From a bis Fmoc-protected selenocystine precursor, multiple avenues of diselenide reduction were attempted to determine the most effective method for subsequent attachment of the protecting group electrophiles. Our previously reported one-pot reduction methodology was ultimately chosen as the optimal approach toward the synthesis of these novel building blocks, and both were easily obtained in high yield and purity. Fmoc-Sec(Xan)-OH was discovered to be bench-stable for extended timeframes while the corresponding Fmoc-Sec(Trt)-OH derivative appeared to detritylate slowly when not stored at -20 °C. Both Sec derivatives were incorporated into single- and multiple-Sec-containing test peptides in order to ascertain the peptides' deprotection behavior and final form upon TFA cleavage. Single-Sec-containing test peptides were always isolated as their corresponding diselenide dimers, while dual-Sec-containing peptide sequences were afforded exclusively as their intramolecular diselenides.
authors.affiliation: Department of Biochemistry, University of Vermont, Room B415 Given Bldg, 89 Beaumont Ave, Burlington, VT 05405, United States.
authors.forename: Stevenson
authors.initials: S
authors.lastname: Flemer
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000138:chemical synthesis*; D005449:Fluorenes / Q000138:chemical synthesis*; D054477:Glutaredoxins / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D009842:Oligopeptides / Q000138:chemical synthesis; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000138:chemical synthesis; D017279:Selenocysteine / Q000031:analogs & derivatives* / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques
chemical_list: D000596:Amino Acids; D005449:Fluorenes; D054477:Glutaredoxins; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D009842:Oligopeptides; D010446:Peptide Fragments; D017279:Selenocysteine
keywords: selenocysteine; sidechain protection; solid phase peptide synthesis; xanthenyl protection