Recent advances in design, synthesis and biological activity of aminoalkylsulfonates and sulfonamidopeptides.
The replacement of peptide bond is an important segment in the synthesis of peptidomimetics, because this modification may result in the preparation of biologically active analogues with improved properties, especially regarding bioavailability and metabolical stability. The introduction of sulfonamide group increases polarity of a molecule and the hydrogen-bond donor properties as a sulfonamide N-H is more acidic (pKa=11-12) than carboxamide. Furthermore, due to geometry of sulfur atom the sulfonamido bond shows structural similarity to the tetrahedral transition state present as an intermediate in the enzymatic hydrolysis of an amide bond thus making these compounds candidates in the development of new drugs. Recent advances in the synthesis of building blocks for sulfonamidopeptides, such as alpha or beta- substituted aminoalkylsulfonates and efficient methods for the formation of sulfonamide bond have enabled the preparation of large number of oligomers with potential applications on various fields. These methods have been applied for the synthesis of oligopeptidosulfonamides, catalysts, receptor molecules and enzyme inhibitors. This article deals with physicochemical properties of sulfonamides, synthesis of aminoalkylsulfonates and sulfonamidopeptides, and the biological activity of these compounds.
Obreza
Ales
A
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, SI-1000 Ljubljana, Slovenia.
Gobec
Stanislav
S
D000476:Alkanesulfonates / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D015195:Drug Design; D006801:Humans; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology*
D000476:Alkanesulfonates; D010446:Peptide Fragments