title: Aqueous microwave-assisted solid-phase peptide synthesis using Fmoc strategy. III: racemization studies and water-based synthesis of histidine-containing peptides.
abstract: In this study, we describe the first aqueous microwave-assisted synthesis of histidine-containing peptides in high purity and with low racemization. We have previously shown the effectiveness of our synthesis methodology for peptides including difficult sequences using water-dispersible 9-fluorenylmethoxycarbonyl-amino acid nanoparticles. It is an organic solvent-free, environmentally friendly method for chemical peptide synthesis. Here, we studied the racemization of histidine during an aqueous-based coupling reaction with microwave irradiation. Under our microwave-assisted protocol using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, the coupling reaction can be efficiently performed with low levels of racemization of histidine. Application of this water-based microwave-assisted protocol with water-dispersible 9-fluorenylmethoxycarbonyl-amino acid nanoparticles led to the successful synthesis of the histidine-containing hexapeptide neuropeptide W-30 (10-15), Tyr-His-Thr-Val-Gly-Arg-NH₂, in high yield and with greatly reduced histidine racemization.
authors: Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Chuo-ku, Kobe, 650-8586, Japan, hojo@pharm.kobegakuin.ac.jp.
authors: Keiko
authors: K
authors: Hojo
authors: Natsuki
authors: N
authors: Shinozaki
authors: Koushi
authors: K
authors: Hidaka
authors: Yuko
authors: Y
authors: Tsuda
authors: Yoshinobu
authors: Y
authors: Fukumori
authors: Hideki
authors: H
authors: Ichikawa
authors: John D
authors: JD
authors: Wade
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D005449:Fluorenes / Q000737:chemistry*; D055772:Green Chemistry Technology; D006639:Histidine / Q000737:chemistry*; D007202:Indicators and Reagents / Q000737:chemistry; D008872:Microwaves; D009025:Morpholines / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry; D009479:Neuropeptides / Q000138:chemical synthesis* / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D060327:Solid-Phase Synthesis Techniques; D012995:Solubility; D013237:Stereoisomerism
chemical_list: C467606:4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; D000596:Amino Acids; D005449:Fluorenes; D007202:Indicators and Reagents; D009025:Morpholines; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; C467731:NPW protein, human; D009479:Neuropeptides; D009842:Oligopeptides; D010446:Peptide Fragments; C000598348:tyrosyl-histidyl-threonyl-valyl-glycyl-argininamide; D006639:Histidine