Glycosidic bond

In chemistry, a glycosidic bond is a type of functional group that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate.

A glycosidic bond is formed between the hemiacetal group of a saccharide (or a molecule derived from a saccharide) and the hydroxyl group of some organic compound such as an alcohol. If the group attached to the carbohydrate residue is not another saccharide it is referred to as an aglycone. If it is another saccharide, the resulting units can be termed as being at the reducing end or the terminal end of the structure. This is a relative nomenclature where the reducing end of the di- or polysaccharide is towards the last anomeric carbon of the structure, and the terminal end is in the opposite direction.

In the literature, the bond between an amino group or other nitrogen-containing group and the sugar is often referred to as a glycosidic bond (although IUPAC seems to suggest that the term is a misnomer). For example, the sugar-base bond in a nucleoside may be referred to as a glycosidic bond.^[1] A substance containing a glycosidic bond is a glycoside.

Formation of ethyl glucoside : Glucose and ethanol combine to form ethyl glucoside and water. The reaction often favors formation of the α glycosidic bond as shown due to the anomeric effect.

Chemistry

The hemiacetal group of carbohydrates (which contains the anomeric carbon) is reactive, and glycosidic bonds form readily in the presence of acid. This is a condensation reaction as one molecule of water is released. This condensation is known as the Fischer glycosidation. Glycosidic bonds are fairly stable; however they can be broken chemically by strong aqueous acids. A glycosidic bond, once formed, is an example of an acetal functional group.

Reducing sugars, those with a free hydroxyl at the anomeric position, in aqueous solution exist in both a minor linear form and a major cyclic form. These forms readily interconvert. Only the cyclic, acetal forms have an anomeric carbon and can form a glycosidic bond; once a glycosidic bond to an aglycone or another carbohydrate residue is formed, the saccharide unit can no longer equilibrate to the linear form without breaking the glycosidic bond.

Polysaccharides

A glycosidic bond can join two monosaccharide molecules to form a disaccharide, as, for instance, in the linkage of glucose and fructose to create sucrose. More complicated polysaccharides such as starch (an important nutrient), glycogen, cellulose (cell walls of plants) or chitin (found in fungi) consist of numerous monosaccharide units joined by glycosidic bonds.

While the cyclic structures of monosaccharide units are fairly rigid, the glycosidic bonds confer flexibility to polysaccharide molecules.

Glycosidic bonds join monosaccharides to form polysaccharides, just like peptide bonds join amino acids to form proteins. The conformation of the torsional angles about the glycosidic bond are the most flexible point of a polysaccharide. The orientations of these torsions typically fall within an expected range of values.

S-, N-, C-, and O-glycosidic bonds

Adenosine, a component of RNA, results from the sugar ribose and adenine via the formation of an N-glycosidic bond (shown as the vertical line between the N and the sugar cycle)

Glycosidic bonds of the form discussed above known as O-glycosidic bonds, in reference to the glycosidic oxygen that links the glycoside to the aglycone or reducing end sugar. In analogy, one also considers S-glycosidic bonds (which form thioglycosides), where the oxygen of the glycosidic bond is replaced with a sulfur atom. In the same way, N-glycosidic bonds, have the glycosidic bond oxygen replaced with nitrogen. Substances containing N-glycosidic bonds are also known as glycosylamines; the term "N-glycoside" is considered a misnomer by IUPAC and is discouraged.^[2] C-glycosyl bonds have the glycosidic oxygen replaced by a carbon. All of these modified glycosidic bonds have different susceptibility to hydrolysis, and in the case of C-glycosyl structures, they are typically more resistant to hydrolysis.

Numbering, and α/β distinction of glycosidic bonds

A β-1,6 glucan molecule showing how carbons are numbered. The terminal saccharide is linked via a β-1,6 glycosidic bond. The remaining linkages are all β-1,3.

One distinguishes between α- and β-glycosidic bonds based on the relative stereochemistry of the anomeric position and the stereocentre furthest from C1 in the saccharide.^[3] In D-hexose sugars in their pyranose forms, an α-glycosidic bond is formed in an axial orientation, whereas a β-glycosidic bond will be oriented equatorially.^[4]

Pharmacologists often join substances to glucuronic acid via glycosidic bonds in order to increase their water solubility; this is known as glucuronidation. Many other glycosides have important physiological functions.

Glycoside hydrolases

Glycoside hydrolases (or glycosidases), are enzymes that break glycosidic bonds. Glycoside hydrolases typically can act either on α- or on β-glycosidic bonds, but not on both.

Before monosaccharide units are incorporated into glycoproteins, polysaccharides, or lipids in living organisms, they are typically first "activated" by being joined via a glycosidic bond to the phosphate group of a nucleotide such as uridine diphosphate (UDP), guanosine diphosphate (GDP), thymidine diphosphate (TDP), or cytidine monophosphate (CMP). These activated biochemical intermediates are known as sugar nucleotides or sugar donors. Many biosynthetic pathways use mono- or oligosaccharides activated by a diphosphate linkage to lipids, such as dolichol. These activated donors are then substrates for enzymes known as glycosyltransferases, which transfer the sugar unit from the activated donor to an accepting nucleophile (the acceptor substrate).

External links

• Definition of glycosides, from the IUPAC Compendium of Chemical Terminology, the "Gold Book"
• Varki A et al. Essentials of Glycobiology. Cold Spring Harbor Laboratory Press; 1999. Searchable online

References