Use of poly(amido)amine dendrimers in prevention of early non-enzymatic modifications of biomacromolecules

Abstract

Hyperglycaemia triggers the formation of both ‘early’ and advanced glycation end products, which are considered the major factors responsible for the complications of diabetes. Poly(amido)amine (PAMAM) dendrimers are relatively new class of materials with unique molecular structure predisposing them for the use as anti-glycation agents. The ability of poly(amido)amine (PAMAM) dendrimers G2 (MW 3256, 120 μmol/l) and G4 (MW 14215, 30 μmol/l) to inhibit the modification of proteins by high glucose (30 mmol/l, 37 °C, 72 h) was investigated using radiometric and spectrofluorometric assays. We monitored (a) non-enzymatic modifications of primary amino groups in BSA and polyamine compounds, and (b) the impact of anti-glycation agents on BSA conformation. Both PAMAM dendrimers and poly( l-lysine) (MW 70 kDa) effectively reduced BSA glycation, while undergoing the time-dependent modification themselves. Such a modification was a function of a number of available free amino groups per molecule, however, both dendrimers and poly( l-lysine) were equally effective in glucose scavenging. PAMAMs neither affected BSA conformation nor formed stable complexes with a protein, while non-glycated poly( l-lysine) significantly quenched BSA fluorescence. Our results encourage raising the hypothesis that PAMAM dendrimers may be considered effective and safe chemical competitors for non-enzymatic modification by glucose, thus confirming the earlier in vivo study showing the inhibition of protein modification in experimental diabetes in the presence of PAMAM dendrimers.