title: Side reactions in the SPPS of Cys-containing peptides.
abstract: Alkylation of sensitive amino acids during synthesis of biologically important peptides is a common and well-documented problem in Fmoc-based strategy. Herein, we probed for the first time an unexpected S-alkylation of Cys-containing peptides that occur during the final TFA cleavage of peptides from the Wang solid support. Through a battery of approaches (NMR, UV and LC-MS) the formed by-product was assigned as the alkylation of the cysteine sulfydryl group by the p-hydroxyl benzyl group derived from the acidic Wang linker decomposition. Factors affecting this side reaction were monitored and a protocol that minimizes the presence of the by-product is reported.
authors: Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioanina, Greece.
authors: Panagiotis
authors: P
authors: Stathopoulos
authors: Serafim
authors: S
authors: Papas
authors: Charalambos
authors: C
authors: Pappas
authors: Vassilios
authors: V
authors: Mousis
authors: Nisar
authors: N
authors: Sayyad
authors: Vassiliki
authors: V
authors: Theodorou
authors: Andreas G
authors: AG
authors: Tzakos
authors: Vassilios
authors: V
authors: Tsikaris
mesh_terms: D000478:Alkylation; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000737:chemistry*; D005449:Fluorenes / Q000737:chemistry; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D060327:Solid-Phase Synthesis Techniques; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D009842:Oligopeptides; D003545:Cysteine