title: Synthesis of linear and cyclic opioid-based peptide analogs containing multiple N-methylated amino acid residues.
abstract: A series of six novel opioid peptide analogs containing one to three N-methylamino acid residues, and six cyclic counterparts of these peptides were prepared by the solid-phase method. Introduction of two consecutive N-methylated amino acids, as well as cyclization of such conformationally constrained sequences, turned out to be challenging. The use of a recently reported triazine-based coupling reagent, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate, enabled the synthesis and cyclization of the designed analogs in acceptable yields and with a lesser amount of by-products than observed with the standard coupling reagents such as TBTU or HATU.
authors.affiliation: Department of Biomolecular Chemistry, Medical University of Lodz, Poland, Mazowiecka 6/8, 92-215, Lodz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Adamska
authors.affiliation: Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Kolesińska
authors.affiliation: Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383, Wroclaw, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Kluczyk
authors.affiliation: Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.
authors.forename: Zbigniew J
authors.initials: ZJ
authors.lastname: Kamiński
authors.affiliation: Department of Biomolecular Chemistry, Medical University of Lodz, Poland, Mazowiecka 6/8, 92-215, Lodz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Janecka
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D015195:Drug Design; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry; D008745:Methylation; D009025:Morpholines / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D018847:Opioid Peptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques; D021241:Spectrometry, Mass, Electrospray Ionization; D013053:Spectrophotometry; D013237:Stereoisomerism; D014227:Triazines / Q000737:chemistry
chemical_list: C000609697:4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate; D000701:Analgesics, Opioid; D007202:Indicators and Reagents; D009025:Morpholines; D009842:Oligopeptides; D018847:Opioid Peptides; D010456:Peptides, Cyclic; D014227:Triazines; C105294:endomorphin 2
keywords: N-methylated amino acids; coupling reagents; cyclization; peptide synthesis