title: N-Terminal 2,3-diaminopropionic acid (Dap) peptides as efficient methylglyoxal scavengers to inhibit advanced glycation endproduct (AGE) formation.
abstract: 2,3-Diaminopropionic acid (Dap) and N-terminal Dap peptides have been found to inhibit in vitro protein-modifications by methylglyoxal (MG), one of the highly reactive alpha-dicarbonyl compounds. MG scavenging potency of the newly synthesized N-terminal Dap peptides is demonstrated by RP-HPLC, SDS-PAGE and non-denaturing PAGE analysis, assays for enzymatic activity and cell viability study and was compared with that of known AGE inhibitors, such as aminoguanidine, pyridoxamine, metformin and carnosine. Two addition products of MG and L-Dap-L-Leu are separated by HPLC and their chemical structures are characterized by (1)H and (13)C NMR spectroscopy to indicate that both of them are pyrazines derived from 2 molecules of MG and 1 molecule of L-Dap-L-Leu. Mutagenic activities of L-Dap-L-Leu and L-Dap-L-Val and their metabolites according to the Ames assay are found to be negative.
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France. andre.sasaki@icsn.cnrs-gif.fr
authors.forename: N André
authors.initials: NA
authors.lastname: Sasaki
authors.forename: Maria Concepcion
authors.initials: MC
authors.lastname: Garcia-Alvarez
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Ludmila
authors.initials: L
authors.lastname: Ermolenko
authors.forename: Gisèle
authors.initials: G
authors.lastname: Franck
authors.forename: Naïma
authors.initials: N
authors.lastname: Nhiri
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Martin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Audic
authors.forename: Pierre
authors.initials: P
authors.lastname: Potier
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000737:chemistry*; D011765:Pyruvaldehyde / Q000737:chemistry*; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D017127:Glycation End Products, Advanced; D010455:Peptides; D015091:beta-Alanine; D011765:Pyruvaldehyde; C011757:2,3-diaminopropionic acid