N-Terminal 2,3-diaminopropionic acid (Dap) peptides as efficient methylglyoxal scavengers to inhibit advanced glycation endproduct (AGE) formation.
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.
Sasaki
N André
NA
Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France. andre.sasaki@icsn.cnrs-gif.fr
Garcia-Alvarez
Maria Concepcion
MC
Wang
Qian
Q
Ermolenko
Ludmila
L
Franck
Gisèle
G
Nhiri
Naïma
N
Martin
Marie-Thérèse
MT
Audic
Nicolas
N
Potier
Pierre
P
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
D017127:Glycation End Products, Advanced; D010455:Peptides; D015091:beta-Alanine; D011765:Pyruvaldehyde; C011757:2,3-diaminopropionic acid