Unusual amino acids accessed through sugar-amino acid hybrids and incorporation into biologically active peptides

Abstract

Sugar-amino acid hybrids are molecules that combine the structural features of simple amino acids with those of simple carbohydrates. The resulting hybrid is a highly substituted, polyfunctionalized building block which can be used to create novel materials with potential applications as glycomimetics, artificial amino acids and peptides. Sugar-amino acid hybrids occur in nature in various forms and are components of several antibacterial, antiviral and antifungal agents. Unnatural sugar-amino acid hybrids can be accessed through incorporation of a carbohydrate-based 5- or 6-membered scaffold into the side chains of amino acids. Additional manipulation on the carbohydrate scaffold may be used to adjust the physical and dynamic properties of the resulting hybrid. Substitution of amino acid building blocks by sugar-amino acid hybrids in peptides allows the engineering of carbohydrate-binding sites into synthetic peptides. This might be a useful route to overcome some of the drawbacks associated with peptide-based drug design such as proteolytic cleavage, poor transport properties, and unselective receptor discrimination.