title: Synthesis of stable isotope-labelled monolysyl advanced glycation endproducts.
abstract: Advanced Glycation Endproducts (AGEs) are modified amino acids that form on proteins and are known to be implicated in the pathogenesis of diabetes and related diseases. Ready access to synthetic stable isotope-labelled AGEs allows for quantitative mass spectrometry studies to be undertaken, providing key insights into the roles AGEs play in the progression of such diseases. However, the majority of current syntheses of these compounds suffer from poor yields and lengthy procedures and are not suitable for the purposes required here. Here, we report robust syntheses of stable isotope-labelled monolysyl AGEs, N(ε)-(carboxymethyl)lysine, N(ε)-(carboxyethyl)lysine and pyrraline, that provide straightforward access to these compounds for quantitative amino acid analysis. This work will facilitate future investigations with these compounds and lead to a better understanding of the roles they play in diabetes and related diseases.
authors.affiliation: School of Chemical Sciences, The University of Auckland, New Zealand.
authors.forename: Tom M
authors.initials: TM
authors.lastname: Woods
authors.forename: Garth J S
authors.initials: GJ
authors.lastname: Cooper
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Brimble
mesh_terms: D003920:Diabetes Mellitus / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000138:chemical synthesis*; D007553:Isotope Labeling / Q000379:methods*; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013058:Mass Spectrometry; D009646:Norleucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D011758:Pyrroles / Q000138:chemical synthesis*
chemical_list: D017127:Glycation End Products, Advanced; D011758:Pyrroles; C054688:N(6)-(1-carboxyethyl)lysine; C048496:N(6)-carboxymethyllysine; C059571:2-formyl-5-(hydroxymethyl)pyrrole-1-norleucine; D009646:Norleucine; D008239:Lysine