title: Methods of the site-selective solid phase synthesis of peptide-derived Amadori products.
abstract: Two procedures of glycated peptides' synthesis have been developed. The first method involves reductive alkylation of the epsilon-amino groups of lysine with 2,3:4,5-di-O-isopropylidene-beta-D-arabino-hexos-2-ulo-2,6-pyranose in the presence of sodium cyanoborohydride on solid support. The second one uses a new fully protected lysine derivative, which is a building block designed for direct introduction of the glycated lysine moiety into a peptide, according to the standard solid phase synthesis protocol. The applicability of the proposed methods for the synthesis of peptide-derived Amadori products is discussed. The structure of the synthesized glycated peptides was confirmed by high-resolution mass spectrometry and enzymatic hydrolysis. Circular dichroism studies, performed in water solution, revealed that the formation of the Amadori rearrangement product in the lysine side chain does not influence significantly the conformational preferences of the peptides studied. However, when the solvent was changed to trifluoroethanol, the glycated peptides preferred beta-turn conformation.
authors.affiliation: Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland. stp@wchuwr.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Stefanowicz
authors.forename: Monika
authors.initials: M
authors.lastname: Kijewska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kapczyńska
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Szewczuk
mesh_terms: D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D005632:Fructose / Q000737:chemistry*; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry; D015416:Maillard Reaction; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012997:Solvents; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D017127:Glycation End Products, Advanced; D009842:Oligopeptides; D010446:Peptide Fragments; D012997:Solvents; D012710:Serum Albumin, Bovine; D005632:Fructose; D008239:Lysine